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EP1161238A1 - Amyotropic lateral sclerosis treatment with a combination of riluzole and an ampa receptor antagonist - Google Patents

Amyotropic lateral sclerosis treatment with a combination of riluzole and an ampa receptor antagonist

Info

Publication number
EP1161238A1
EP1161238A1 EP00910920A EP00910920A EP1161238A1 EP 1161238 A1 EP1161238 A1 EP 1161238A1 EP 00910920 A EP00910920 A EP 00910920A EP 00910920 A EP00910920 A EP 00910920A EP 1161238 A1 EP1161238 A1 EP 1161238A1
Authority
EP
European Patent Office
Prior art keywords
imidazo
indeno
pyrazine
dihydro
alk
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00910920A
Other languages
German (de)
French (fr)
Inventor
Andrees Bohme
Alain Boireau
Thierry Canton
Jérémy Pratt
Jean-Marie Stutzmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
Aventis Pharma SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from FR9903100A external-priority patent/FR2790670A1/en
Application filed by Rhone Poulenc Rorer SA, Aventis Pharma SA filed Critical Rhone Poulenc Rorer SA
Publication of EP1161238A1 publication Critical patent/EP1161238A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to the prevention and / or treatment of amyotropic lateral sclerosis with a combination of riluzole or a pharmaceutically acceptable salt thereof and one or more antagonists of AMPA receptors (alpha-amino-4-hydroxy-5 -methylisoxazole-4-propionate), the new combinations and the pharmaceutical compositions containing them.
  • AMPA receptors alpha-amino-4-hydroxy-5 -methylisoxazole-4-propionate
  • ALS Amyotrophic lateral sclerosis
  • Charcot disease Lou Gehrig's disease
  • Lou Gehrig's disease is a fatal disease resulting from the degeneration of motor neurons. The disease is accompanied by progressive paralysis leading to the complete loss of motor and respiratory functions and then to death within 2 to 8 years after the onset of symptoms (3 years on average).
  • This compound is also useful as an anticonvulsant, anxiolytic and hypnotic (EP50551), in the treatment of schizophrenia (EP305276), in the treatment of sleep disorders and depression (EP305277), in the treatment of cerebrovascular disorders and as an anesthetic (EP282971), in the treatment of spinal, cranial or cranio-spinal trauma (W094 / 13288), as a radiorestaurator (WO94 / 15600), in the treatment of Parkinson's disease (WO94 / 15601) neuro-AIDS (WO94 / 20103), in the treatment of mitochondrial diseases (WO95 / 19170).
  • AMPA receptor antagonists are recommended as neuroprotectors (R. GILL and D.
  • the combination may also contain a mixture of AMPA receptor antagonists.
  • salts of riluzole may be mentioned in particular the addition salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethio- nate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphtoate or substitution derivatives of these derivatives.
  • mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethio- nate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphtoate or substitution derivatives of these derivatives.
  • AMPA receptor antagonists those of the class are preferred.
  • R3 represents a hydrogen atom or a carboxy, alkoxycarbonyl or carboxamido radical
  • - R4 represents an alkyl, -alk-Het or phenylalkyl radical in which the phenyl nucleus is optionally substituted by one or more substituents chosen from located among halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR- radicals
  • - R5 represents an alkyl radical (1-11C in a straight or branched chain), -alk-Het, -NR 8 Rg, -NH-CHO, -NH-COOR 17 , -NH-SO2R24, -COOR10, -alk-COOR -io, -alk-CONR ⁇ nRl8> -alk-NR 10 Ri8.
  • - Rg represents a hydrogen atom or a hydroxy radical, alkyl (1-11C in straight or branched chain), -alk-OH, -NR14R15, -alk-NR ⁇ Ris, -alk-Het, -NH-CHO, -COOalk, -alk-COOR-jo.
  • oR2l phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2 radicals, -COOR-
  • R7 represents an oxygen atom or a NOH, NO-alk-COOR-jo, NO-alk, CHR-19, NR10 C (COOR-
  • - R ⁇ represents a hydrogen atom or an alkyl radical, -alk-COOR-jo, -alk-NR-
  • Rg represents a hydrogen atom or an alkyl radical
  • R10 represents a hydrogen atom or an alkyl radical
  • 1 represents a hydrogen atom or an alkyl radical (1-9C in a straight or branched chain), -alk-COOR-io, -alk-Het, -alk-NR-j2Rio ⁇ phenylalkyl in which the phenyl nucleus is optionally substituted by one or more killing agents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR-
  • R-J2 represents a hydrogen atom or an alkyl radical
  • - R-) 3 represents an alkyl, Het or alkoxycarbonyl radical
  • R-14 and R- 5, identical or different, each represent an alkyl radical or else R-14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl radical, -COR22. -CSR23 or -SO2R24.
  • 6 represents a chain -CHOH- or -CH (OH) -alk (1-5C) -,
  • R-17 represents an alkyl or phenylalkyl radical
  • Ris represents a hydrogen atom or an alkyl radical
  • - R19 represents a hydroxy, alkyl, -alk-Het, -NR25R26- -alk-COORio, -Het, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino radicals , hydroxy, -alk-NH2, -COOR ⁇ Q.
  • R20 represents a hydrogen atom or an alkyl radical
  • - R21 represents a hydrogen atom or an alkyl radical
  • - R22 represents an alkyl, cycloalkyl, -COOalk, -alk-COOR-
  • o phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk radicals -NH2, -COOR-I Q, cyano and -alk-COOR-iQ, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy radicals , -alk-NH2, -COOR-
  • - R23 represents a radical -NH-alk, -NH-Ar, -NH-Het or -NH2,
  • R24 represents an alkyl or phenyl radical
  • R25 and R26 identical or different, each represent an alkyl or cycloalkyl radical
  • R27 represents a hydrogen atom or an alkyl radical
  • alk represents an alkyl or alkylene radical
  • Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms (O, S, N) optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
  • the alkyl, alkylene and alkoxy radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain
  • the acyl radicals and portions contain 2 to 4 carbon atoms
  • the cycloalkyl radicals contain 3 to 6 carbon atoms
  • the halogen atoms are chosen from fluorine, chlorine, bromine and iodine.
  • Het is chosen from pyrrolyl rings optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals, pyridyl optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals, pyrimidinyl optionally substituted by one or more alkyl, phenyl radicals or phenylalkyl, imidazolyl optionally substituted by one or more alkyl, phenyl or phenylalkyl, thiazolyl radical optionally substituted by one or more alkyl, phenyl or phenylalkyl, oxazolinyl radical optionally substituted by one or more alkyl, phenyl or phenylalkyl, thiazolinyl radical optionally substituted by or more alkyl, phenyl or phenylalkyl, pyrazinyl radicals optionally substituted by one or more alkyl,
  • the compounds of formula (I) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
  • the compounds of formula (I) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
  • salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis- ⁇ - oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl- ⁇ -phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
  • mineral or organic acids such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theo
  • - R ' represents a hydrogen atom or a carboxy, alkoxycarbonyl, -CO-NR'4R'5, -PO3H2 or -CH2OH radical,
  • - R'- represents a radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR ' 5 R'g or -CO-NH-R' 7 ,
  • R'3 represents an alkyl, phenyl, phenylalkyl, cycloalkyl or -NR'gR's radical
  • R'4 represents a hydrogen atom or an alkyl radical
  • R'5 represents a hydrogen atom or an alkyl, phenyl, cycloalkyl or phenylalkyl radical
  • R'g represents a hydrogen atom or an alkyl radical, or else R'5 and R'g form, with the nitrogen atom to which they are attached, a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 6 carbon atoms and optionally one or more other heteroatoms chosen from O, S, N ,
  • R'7 represents a phenyl, phenylalkyl or -alk-COOR'4 radical
  • R'g represents a hydrogen atom or an alkyl, cycloalkyl or phenylalkyl radical
  • alk represents an alkyl or alkylene radical
  • alkoxy, alkyl and alkylene radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain and the cycloalkyl radicals contain 3 to 6 carbon atoms.
  • R′5 and R′g form with the nitrogen atom to which they are attached a heterocycle
  • the latter is chosen from the azetidine, pyrrolidine, piperidine, piperazine and morpholine rings.
  • is in position -8 or -9.
  • the compounds of formula (la) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
  • the compounds of formula (la) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
  • pharmaceutically acceptable salts there may be mentioned addition salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis- ⁇ - oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl- ⁇ -phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
  • mineral or organic acids such as a
  • the preferred compounds of formula (la) are the following:
  • R "1 represents a radical -alk-CN, -alk-COOH, -alk-Het", -alk-P03H2 or -alk-C0-NH-S02R "2,
  • R "2 represents an alkyl or phenyl radical
  • alk represents an alkyl radical
  • Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms chosen from O, S, N, the heterocycle being optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
  • alkyl and alkoxy radicals contain 1 to 6 carbon atoms in a straight or branched chain.
  • the substituent R "1 is in position -8 or -9.
  • Het represents a tetrazole-5-yl ring.
  • the compounds of formula (Ib) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
  • the compounds of formula (Ib) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
  • salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis- ⁇ - oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl- ⁇ -phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
  • mineral or organic acids such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theo
  • R "'represents a radical C (R"' 4) R '" 5 , CH-R"' g or C R '" 7 ,
  • and R'" identical or different, represent hydrogen or halogen atoms or amino, nitro or -NH-CO-NR "" -
  • R '"5 represents a radical -alk-COOR'" -
  • R "'g represents a hydrogen atom or a radical -NR"' -
  • R '"7 represents a NOH or C (COOR"' -
  • o represents a hydrogen atom or an alkyl radical
  • R "'i2 represents a hydrogen atom
  • R "'i5 represents a hydrogen atom or a radical -COR'" 22.
  • - R '"22 represents an alkyl radical
  • - alk represents an alkyl radical
  • alkyl radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain and the halogen atoms are chosen from fluorine, chlorine, bromine and iodine.
  • the compounds of formula (Ie) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
  • the compounds of formula (Ic) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
  • salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis- ⁇ - oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl- ⁇ -phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
  • mineral or organic acids such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theo
  • the following compounds are preferred: 1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, 8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, acid (5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-5-yl) acetic,
  • the AMPA receptor antagonist is a selective antagonist, that is to say that this compound is at least 20 times more active on AMPA receptors than on other glutamate receptors and, in particular, the NMDA receptor, and generally 50 and even 100 times more active.
  • transgenic mice which constitute a model of ALS according to the following test : transgenic mice (B6SJL-TgN (SOD1-G93A, G1H) heterozygous for the mutated gene coding for a pathological SOD1 found in certain cases of ALS are divided into 4 groups A, B, C and D.
  • the animals in group A are control animals and receive only 25 ml / kg of saline solution (0.9%) subcutaneously once a day.
  • the animals of groups B are treated from the 50 th day of life with 200 ⁇ g / ml of riluzole in the drinking water available ad libitum until death (consumption is of the order of 3 to 3.5 ml / mouse / day).
  • the animals of group C are treated from the 42nd day of life with 3 mg / kg / day by the subcutaneous route of the AMPA receptor antagonist in saline solution until death.
  • the animals of group D are treated from the 42nd day of life with 3 mg / kg / day by subcutaneous route of the AMPA receptor antagonist in saline solution and from the 50th day of life with 200 ⁇ g / ml riluzole in drinking water until death.
  • the compounds of the combination can be used orally, parenterally, transdermally or rectally either simultaneously or separately or spread out over time.
  • the preferred combinations are those which contain one of the AMPA receptor antagonists mentioned above, with the exception of GYKI52466 and CNQX.
  • the present invention also relates to pharmaceutical compositions comprising the combination of riluzole and one or more AMPA receptor antagonists with the exception of GYKI52466 and CNQX, in the pure state or in the form of a combination with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants and / or optionally in combination with another pharmaceutically compatible and physiologically active product.
  • compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
  • the active ingredients are mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
  • these compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.
  • compositions for oral administration there may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
  • inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
  • These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
  • the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
  • solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or the like, can be used. suitable organic solvents.
  • These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions. riles which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
  • compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
  • the present invention also relates to the method of prevention and / or treatment of patients suffering from amyotrophic lateral sclerosis which consists in administering to the patient a combination of riluzole or one of its pharmaceutically acceptable salts and of one or more antagonists of AMPA receptors, either simultaneously either separately or spread out over time.
  • the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally from 10 to 400 mg per day orally for an adult with unit doses ranging from 10 to 200 mg of riluzole and from 5 to 100 mg per day by subcutaneous or transdermal route for an adult with unit doses of 1 to 50 mg of the AMPA receptor antagonist.
  • the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.

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Abstract

The invention concerns the prevention and/or treatment of amyotropic lateral sclerosis with a combination of riluzole and one or several AMPA receptor antagonists, the novel combinations and the pharmaceutical compositions containing them.

Description

TRAITEMENT DE LA SCLEROSE LATERALE AMYOTROPHIQUE AVEC UNE ASSOCIATION DE RILUZOLE ET D 'UN ANTAGONISTE DES RECEPTEURS AMPATREATMENT OF AMYOTROPHIC SIDE SCLEROSIS WITH A COMBINATION OF RILUZOLE AND AN AMPA RECEPTOR ANTAGONIST
5 La présente invention concerne la prévention et/ou le traitement de la sclérose latérale amyotrop ique avec une association du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA (alpha-amino-4-hydroxy-5-méthylisoxazole-4- propionate), les nouvelles associations et les compositions pharmaceutiques 0 les contenant.The present invention relates to the prevention and / or treatment of amyotropic lateral sclerosis with a combination of riluzole or a pharmaceutically acceptable salt thereof and one or more antagonists of AMPA receptors (alpha-amino-4-hydroxy-5 -methylisoxazole-4-propionate), the new combinations and the pharmaceutical compositions containing them.
La sclérose latérale amyotrophique (SLA) connue également sous le nom de maladie de Charcot ou maladie de Lou Gehrig est une maladie mortelle résultant de la dégénérescence des motoneurones. La maladie s'accompagne d'une paralysie progressive conduisant à la perte totale des fonctions motri- 5 ces et respiratoires puis à la mort dans un délai de 2 à 8 ans après l'apparition des symptômes (3 ans en moyenne).Amyotrophic lateral sclerosis (ALS) also known as Charcot disease or Lou Gehrig's disease is a fatal disease resulting from the degeneration of motor neurons. The disease is accompanied by progressive paralysis leading to the complete loss of motor and respiratory functions and then to death within 2 to 8 years after the onset of symptoms (3 years on average).
A ce jour, seul le riluzole (2-amino-6-trifluorométhoxybenzothiazole) est commercialisé sous le nom de RilutekR pour le traitement de la sclérose latérale amyotrophique.To date, only riluzole (2-amino-6-trifluoromethoxybenzothiazole) is marketed under the name of Rilutek R for the treatment of amyotrophic lateral sclerosis.
0 Ce composé est également utile comme anticonvulsivant, anxiolytique et hypnotique (EP50551), dans le traitement de la schizophrénie (EP305276), dans le traitement des troubles du sommeil et de la dépression (EP305277), dans le traitement des désordres cérébrovasculaires et comme anesthésique (EP282971 ), dans le traitement des traumatismes spinaux, crâniens ou crâ- 5 nio-spinaux (W094/13288), comme radiorestaurateur (WO94/15600), dans le traitement de la maladie de Parkinson (WO94/15601), dans le traitement du neuro-sida (WO94/20103), dans le traitement des maladies mitochondriales (WO95/19170). Les antagonistes des récepteurs AMPA sont préconisés comme neuroprotecteurs (R. GILL et D. LODGE, International Review of Neorobiology, 40, 197-232 (1997)) et pour la prévention et/ou le traitement de la maladie de Parkinson (T. Klockgether et coll., Ann. Neurol., 30, 717 (1991); brevet W09211012).0 This compound is also useful as an anticonvulsant, anxiolytic and hypnotic (EP50551), in the treatment of schizophrenia (EP305276), in the treatment of sleep disorders and depression (EP305277), in the treatment of cerebrovascular disorders and as an anesthetic (EP282971), in the treatment of spinal, cranial or cranio-spinal trauma (W094 / 13288), as a radiorestaurator (WO94 / 15600), in the treatment of Parkinson's disease (WO94 / 15601) neuro-AIDS (WO94 / 20103), in the treatment of mitochondrial diseases (WO95 / 19170). AMPA receptor antagonists are recommended as neuroprotectors (R. GILL and D. LODGE, International Review of Neorobiology, 40, 197-232 (1997)) and for the prevention and / or treatment of Parkinson's disease (T. Klockgether et al., Ann. Neurol., 30, 717 (1991); patent W09211012).
Une association de riluzole et du GYKI52466 a été utilisée dans un test de comportement moteur chez le rat (BD. KRETSCHMER et coll., Naunym- Schmiedeberg's Arch. Pharmacol., 358, 181-190 (1998)). Par ailleurs, les effets du riluzole dans un test de lésion induite par FeCI3 en présence de CNQX ont été décrits par JY KOH et coll, Journal of Neurochemistry, 72 (2), 716-723 (1999).A combination of riluzole and GYKI52466 was used in a motor behavior test in rats (BD. KRETSCHMER et al., Naunym-Schmiedeberg's Arch. Pharmacol., 358, 181-190 (1998)). Furthermore, the effects of riluzole in a test for damage induced by FeCI 3 in the presence of CNQX have been described by JY KOH et al, Journal of Neurochemistry, 72 (2), 716-723 (1999).
Il a maintenant été trouvé de façon surprenante que l'association du riluzole ou un sel pharmaceutiquement acceptable de celui-ci avec un antagoniste des récepteurs AMPA présente un effet synergisant dans la prévention et/ou le traitement de la sclérose latérale amyotrophique.It has now surprisingly been found that the combination of riluzole or a pharmaceutically acceptable salt thereof with an AMPA receptor antagonist has a synergistic effect in the prevention and / or treatment of amyotrophic lateral sclerosis.
Il a en effet été découvert qu'avec une telle association, la durée de vie est prolongée de manière significative.It has indeed been discovered that with such an association, the lifespan is significantly extended.
L'association peut également contenir un mélange d'antagonistes des récepteurs AMPA.The combination may also contain a mixture of AMPA receptor antagonists.
Comme sels pharmaceutiquement acceptables du riluzole peuvent être notamment cités les sels d'addition avec les acides minéraux tels que chlorhydrate, sulfate, nitrate, phosphate ou organiques tels que acétate, propionate, succinate, oxalate, benzoate, fumarate, maléate, méthanesulfonate, iséthio- nate, théophilline-acétate, salicylate, phénolphtalinate, méthy- lène-bis-β-oxynaphtoate ou des dérivés de substitution de ces dérivés.As pharmaceutically acceptable salts of riluzole may be mentioned in particular the addition salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethio- nate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis-β-oxynaphtoate or substitution derivatives of these derivatives.
Parmi les antagonistes des récepteurs AMPA, sont préférés ceux de la classe 1 - des dérivés de 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one de formule :Among the AMPA receptor antagonists, those of the class are preferred. 1 - 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one derivatives of formula:
dans laquellein which
- R représente un radical N-alk, C(R4)R5, CH-Rβ ou C=Ry,- R represents an N-alk, C (R4) R5, CH-Rβ or C = Ry radical,
- R-| et R2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux alkyle, alcoxy, amino, -N=CH-N(alk)alk', nitro, cyano, phényle, imidazolyle, SO3H, hydroxy, polyfluoroalcoxy, carboxy, al- coxycarbonyle, -NH-CO-NR11 R-| 2, -N(alk)-CO-NRι 1 R-| 2. -N(alk-Ar)-CO-NR1 1 R12, -NH-CS-NR-| -| Rι2, -N(alk)-CS-NR-| i R-|2,- R- | and R2, identical or different, represent hydrogen or halogen atoms or alkyl, alkoxy, amino, -N = CH-N (alk) alk ', nitro, cyano, phenyl, imidazolyl, SO3H, hydroxy, polyfluoroalkoxy, carboxy, alkoxycarbonyl, -NH-CO-NR11 R- | 2, -N (alk) -CO-NRι 1 R- | 2. -N (alk-Ar) -CO-NR 1 1 R 12 , -NH-CS-NR- | - | Rι 2 , -N (alk) -CS-NR- | i R- | 2,
-NH-CO-R-i 1 , -NH-CS-R24, -NH-C(=NR27)-NR-ι 0Rι 2. -CO-NR-|0Ri2. -NH-SO2-NR10Ri2.-NH-CO-Ri 1, -NH-CS-R24, -NH-C (= NR 2 7) -NR-ι 0 Rι 2. -CO-NR- | 0 Ri2. -NH-SO 2 -NR 10 Ri2.
-N(alk)-Sθ2-NR10R12- -NH-S02-CF3, -NH-S02-alk, -NR10R13, -S(0)m-alk-Ar, -S02-NR-| QRI2> 2-oxo-1-imidazolidinyle dont la position -3 est éventuellement substituée par un radical alkyle ou 2-OXO-1 -perhydropyrimidinyle dont la position -3 est éventuellement substituée par un radical alkyle,-N (alk) -Sθ2-NR 10 R12- -NH-S0 2 -CF 3 , -NH-S02-alk, -NR10R13, -S (0) m -alk-Ar, -S02-NR- | QRI2 > 2-oxo-1-imidazolidinyl whose position -3 is optionally substituted by an alkyl radical or 2-OXO-1 -perhydropyrimidinyl whose position -3 is optionally substituted by an alkyl radical,
- R3 représente un atome d'hydrogène ou un radical carboxy, alcoxycarbo- nyle ou carboxamido,- R3 represents a hydrogen atom or a carboxy, alkoxycarbonyl or carboxamido radical,
- R4 représente un radical alkyle, -alk-Het ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choi- sis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-| Q et -alk-COOR-|o.- R4 represents an alkyl, -alk-Het or phenylalkyl radical in which the phenyl nucleus is optionally substituted by one or more substituents chosen from located among halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR- radicals | Q and -alk-COOR- | o.
- R5 représente un radical alkyle (1-11C en chaîne droite ou ramifiée), -alk-Het, -NR8Rg, -NH-CHO, -NH-COOR17, -NH-SO2R24, -COOR10, -alk-COOR-io, -alk-CONRιnRl8> -alk-NR10Ri8. -alk-OH, -alk-CN, phénylal- kyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-IQ et -alk-COOR-|o> -NH-CO-Ar dont Ar est éventuellement substitué par un ou plusieurs substi- tuants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-10 et -alk-COOR-|o. -NH-CO-Het, -NH-CO-alk-Het, -NH-CO-alk-COOR10, -NH-CO-alk-NR 0Ri8. -NH-CO-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-IQ et -alk-COOR-io. pyrrol-1-yle éventuellement substitué par un radical -COOR10. -NH-CO-NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COOR-|o. -NH-CO-NH-Het, -NH-CO-NH-alk-Het, -NH-CO-NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 et -alk-COOR-io, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH-alk ou -NH-CO-NH2,- R5 represents an alkyl radical (1-11C in a straight or branched chain), -alk-Het, -NR 8 Rg, -NH-CHO, -NH-COOR 17 , -NH-SO2R24, -COOR10, -alk-COOR -io, -alk-CONRιnRl8> -alk-NR 10 Ri8. -alk-OH, -alk-CN, phenylalkyl, the phenyl nucleus of which is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk- radicals NH2, -COOR-IQ and -alk-COOR- | o > -NH-CO-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino radicals , hydroxy, cyano, -alk-NH2, -COOR-10 and -alk-COOR- | o. -NH-CO-Het, -NH-CO-alk-Het, -NH-CO-alk-COOR 10 , -NH-CO-alk-NR 0 Ri8. -NH-CO-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-IQ and -alk-COOR-io. pyrrol-1-yl optionally substituted with a radical -COOR10. -NH-CO-NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR- radicals I Q and -alk-COOR- | o. -NH-CO-NH-Het, -NH-CO-NH-alk-Het, -NH-CO-NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl radicals, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 and -alk-COOR-io, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH-alk or -NH-CO-NH2 ,
ou bien R4 et R5 forment ensemble avec l'atome de carbone auquel ils sont rattachés (a) un cycle 2- ou 3-ρyrrolidine, un cycle 2- ou 4-pipéridine ou un cycle 2-azacycloheptane, ces cycles étant éventuellement substitués sur l'azote par un radical alkyle, -CHO, -COORn , -CO-alk-COOR6, -CO-alk-NR62, -CO-alk-CONR6R8, -CO-COOR6, -CO-CH2-0-CH2-COOR6, -CO-CH2-S-CH -COOR6, -CO-CH=CH-COOR6, -CO-alk, -CO-Ar", -CO-alk-Ar", -CO-NH-Ar", -CO-NH-alk-Ar", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH2, -CO-NH-alk, -CO-N(alk)alk', -CS-NH2, -CS-NH-alk, -CS-NH-Ar", -CS-NH-Het, -alk-Het, -alk-NReRβ, -alk-COORg, -alk-CO-NRβRs, -alk-Ar", -Sθ2-alk, -Sθ2-Ar ou -CO-cycloalkyle dont le cycloalkyle est éventuellement substitué en -2 par un radical carboxy, (b) un cycle 2-pyrrolidine-5-one ou (c) un cycloalkyle,or else R4 and R5 form together with the carbon atom to which they are attached (a) a 2- or 3-ρyrrolidine ring, a 2- or 4-piperidine ring or a 2-azacycloheptane ring, these rings being optionally substituted on nitrogen by an alkyl radical, -CHO, -COORn, -CO-alk-COOR6, -CO-alk-NR 62 , -CO-alk-CONR 6 R 8 , -CO-COOR6, -CO-CH 2 -0-CH2-COOR 6 , -CO-CH2-S-CH -COOR 6 , -CO-CH = CH-COOR 6 , -CO-alk, -CO-Ar ", -CO-alk -Ar ", -CO-NH-Ar", -CO-NH-alk-Ar ", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH 2 , -CO-NH-alk, -CO-N (alk) alk ', -CS-NH 2 , -CS-NH-alk, -CS-NH-Ar ", -CS-NH-Het , -alk-Het, -alk-NReRβ, -alk-COORg, -alk-CO-NRβRs, -alk-Ar ", -Sθ2-alk, -Sθ2-Ar or -CO-cycloalkyle the cycloalkyl of which is optionally substituted -2 with a carboxy radical, (b) a 2-pyrrolidine-5-one ring or (c) a cycloalkyl,
- Rg représente un atome d'hydrogène ou un radical hydroxy, alkyle (1-11C en chaîne droite ou ramifiée), -alk-OH, -NR14R15, -alk-NR^Ris, -alk-Het, -NH-CHO, -COOalk, -alk-COOR-jo. -alk-CO-NR-|oR2l , phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-|Q et -alk-COOR-|o> -R16-COOR10, -CO-COOR-io, pyrrol-1-yle éventuellement substitué par un radical -COOR-J Q ou 2-oxo-2,5-dihydropyrrol-1-yle,- Rg represents a hydrogen atom or a hydroxy radical, alkyl (1-11C in straight or branched chain), -alk-OH, -NR14R15, -alk-NR ^ Ris, -alk-Het, -NH-CHO, -COOalk, -alk-COOR-jo. -alk-CO-NR- | oR2l, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2 radicals, -COOR- | Q and -alk-COOR- | o> -R16-COOR10, -CO-COOR-io, pyrrol-1-yl optionally substituted by a radical -COOR-J Q or 2-oxo-2,5- dihydropyrrol-1-yle,
- R7 représente un atome d'oxygène ou un radical NOH, NO-alk-COOR-jo, NO-alk, CHR-19, NR10 C(COOR-|o)R20 ou C(CONRI QR21 )R20.- R7 represents an oxygen atom or a NOH, NO-alk-COOR-jo, NO-alk, CHR-19, NR10 C (COOR- | o) R20 or C (CONRI QR21) R 20 radical.
- Rβ représente un atome d'hydrogène ou un radical alkyle, -alk-COOR-jo, -alk-NR-|()R21. -alk-Het ou phénylalkyle dont le noyau phényle est éventuel- lement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-io et -alk-COOR-|o.- Rβ represents a hydrogen atom or an alkyl radical, -alk-COOR-jo, -alk-NR- | () R21. -alk-Het or phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH 2 , -COOR radicals -io and -alk-COOR- | o.
- Rg représente un atome d'hydrogène ou un radical alkyle,- Rg represents a hydrogen atom or an alkyl radical,
- R10 représente un atome d'hydrogène ou un radical alkyle,- R10 represents a hydrogen atom or an alkyl radical,
- R-| 1 représente un atome d'hydrogène ou un radical alkyle (1-9C en chaîne droite ou ramifiée), -alk-COOR-io, -alk-Het, -alk-NR-j2Rio< phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substi- tuants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-|o, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-io ou -Het,- R- | 1 represents a hydrogen atom or an alkyl radical (1-9C in a straight or branched chain), -alk-COOR-io, -alk-Het, -alk-NR-j2Rio <phenylalkyl in which the phenyl nucleus is optionally substituted by one or more killing agents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR- | o, phenyl radicals optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR-io or -Het radicals,
- R-J2 représente un atome d'hydrogène ou un radical alkyle,- R-J2 represents a hydrogen atom or an alkyl radical,
- R-)3 représente un radical alkyle, Het ou alcoxycarbonyle,- R-) 3 represents an alkyl, Het or alkoxycarbonyl radical,
- R-14 et R-|5, identiques ou différents représentent chacun un radical alkyle ou bien R-14 représente un atome d'hydrogène et R15 représente un atome d'hydrogène ou un radical alkyle, -COR22. -CSR23 ou -SO2R24.- R-14 and R- | 5, identical or different, each represent an alkyl radical or else R-14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl radical, -COR22. -CSR23 or -SO2R24.
- R-|6 représente une chaîne -CHOH- ou -CH(OH)-alk(1-5C)-,- R- | 6 represents a chain -CHOH- or -CH (OH) -alk (1-5C) -,
- R-17 représente un radical alkyle ou phénylalkyle,- R-17 represents an alkyl or phenylalkyl radical,
- Ris représente un atome d'hydrogène ou un radical alkyle,Ris represents a hydrogen atom or an alkyl radical,
- R19 représente un radical hydroxy, alkyle, -alk-Het, -NR25R26- -alk-COORio, -Het, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR^ Q. cyano et -alk-COOR-io ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-jo. cyano et -alk-COOR-10,- R19 represents a hydroxy, alkyl, -alk-Het, -NR25R26- -alk-COORio, -Het, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino radicals , hydroxy, -alk-NH2, -COOR ^ Q. cyano and -alk-COOR-10 or phenylalkyl in which the phenyl ring is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro radicals , amino, hydroxy, -alk-NH2, -COOR-jo. cyano and -alk-COOR-10,
- R20 représente un atome d'hydrogène ou un radical alkyle,- R20 represents a hydrogen atom or an alkyl radical,
- R21 représente un atome d'hydrogène ou un radical alkyle, - R22 représente un radical alkyle, cycloalkyle, -COOalk, -alk-COOR-|o, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano et -alk-COOR-iQ, phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-| Q, cyano et -alk-COOR-|Q, -NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-IQ, cyano et -alk-COOR-iQ, -Het, -alk-Het, -OR-17, -NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR10, cyano et -alk-COOR-io, -NH-alk-Het, -NH-alk, -NH2 ou -NH-Het,- R21 represents a hydrogen atom or an alkyl radical, - R22 represents an alkyl, cycloalkyl, -COOalk, -alk-COOR- | o, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk radicals -NH2, -COOR-I Q, cyano and -alk-COOR-iQ, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy radicals , -alk-NH2, -COOR- | Q, cyano and -alk-COOR- | Q, -NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-IQ, cyano and -alk-COOR radicals -iQ, -Het, -alk-Het, -OR-17, -NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino radicals, hydroxy, -alk-NH2, -COOR10, cyano and -alk-COOR-io, -NH-alk-Het, -NH-alk, -NH 2 or -NH-Het,
- R23 représente un radical -NH-alk, -NH-Ar, -NH-Het ou -NH2,- R23 represents a radical -NH-alk, -NH-Ar, -NH-Het or -NH2,
- R24 représente un radical alkyle ou phényle,- R24 represents an alkyl or phenyl radical,
- R25 et R26, identiques ou différents, représentent chacun un radical alkyle ou cycloalkyle,- R25 and R26, identical or different, each represent an alkyl or cycloalkyl radical,
- R27 représente un atome d'hydrogène ou un radical alkyle,- R27 represents a hydrogen atom or an alkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
- alk' représente un radical alkyle,- alk 'represents an alkyl radical,
- m est égal à 0, 1 ou 2,- m is equal to 0, 1 or 2,
- Ar représente un radical phényle,- Ar represents a phenyl radical,
- Het représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes (O, S, N) éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle,- Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms (O, S, N) optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
les isomères (E et Z) et leurs mélanges des composés pour lesquels R7 représente un radical NO-alk, C(COOR-|o)R2θ) C(CONR-| QR2-| )R20 OU CHR-|9, les formes tautomères (E et Z) des composés pour lesquels R représente un radical CH-Rg et Rg représente un radical -CO-COOR-| Q, les énantiomères et diastéréoisomères des composés pour lesquels R représente un radical C(R4)R5 ou CH-Rgthe isomers (E and Z) and their mixtures of the compounds for which R7 represents a radical NO-alk, C (COOR- | o) R2θ ) C (CONR- | QR2- |) R20 OR CHR- | 9, the tautomeric forms (E and Z) of the compounds for which R represents a CH-Rg radical and Rg represents a -CO-COOR- radical | Q, the enantiomers and diastereoisomers of the compounds for which R represents a radical C (R4) R5 or CH-Rg
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
Sauf mention contraire, dans les définitions qui précédent, les radicaux et portions alkyle, alkylène et alcoxy contiennent 1 à 6 atomes de carbone et sont en chaîne droite ou ramifiée, les radicaux et portions acyle contiennent 2 à 4 atomes de carbone, les radicaux cycloalkyle contiennent 3 à 6 atomes de carbone et les atomes d'halogène sont choisis parmi le fluor, le chlore, le brome et l'iode.Unless otherwise stated, in the definitions above, the alkyl, alkylene and alkoxy radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain, the acyl radicals and portions contain 2 to 4 carbon atoms, the cycloalkyl radicals contain 3 to 6 carbon atoms and the halogen atoms are chosen from fluorine, chlorine, bromine and iodine.
De préférence, Het est choisi parmi les cycles pyrrolyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, pyri- dyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, pyrimidinyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, imidazolyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, thiazolyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, oxazolinyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, thiazolinyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, pyrazinyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, tétrazolyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle ou triazolyle éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle. Les substituants préférés sont les radicaux méthyle, phényle et benzyle.Preferably, Het is chosen from pyrrolyl rings optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals, pyridyl optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals, pyrimidinyl optionally substituted by one or more alkyl, phenyl radicals or phenylalkyl, imidazolyl optionally substituted by one or more alkyl, phenyl or phenylalkyl, thiazolyl radical optionally substituted by one or more alkyl, phenyl or phenylalkyl, oxazolinyl radical optionally substituted by one or more alkyl, phenyl or phenylalkyl, thiazolinyl radical optionally substituted by or more alkyl, phenyl or phenylalkyl, pyrazinyl radicals optionally substituted by one or more alkyl, phenyl or phenylalkyl, tetrazolyl radicals optionally substituted by one or more alkyl, phenyl or phenylalkyl or triazolyl radicals optionally are substituted by one or more alkyl, phenyl or phenylalkyl radicals. Preferred substituents are methyl, phenyl and benzyl.
Les composés de formule (I) comportant un reste basique peuvent être éventuellement transformés en sels d'addition avec un acide minéral ou or- ganique.The compounds of formula (I) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
Les composés de formule (I) comportant un reste acide peuvent éventuellement être transformés en sels métalliques ou en sels d'addition avec les bases azotées.The compounds of formula (I) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
Comme exemples de sels pharmaceutiquement acceptables, peuvent être cités les sels d'addition avec les acides minéraux ou organiques (tels que acétate, propionate, succinate, benzoate, fumarate, maléate, oxalate, mé- thanesulfonate, iséthionate, théophyllinacétate, salicylate, méthylène-bis-β- oxynaphtoate, chlorhydrate, sulfate, nitrate et phosphate), les sels avec les métaux alcalins (sodium, potassium, lithium) ou avec les métaux alcalinoter- reux (calcium, magnésium), le sel d'ammonium, les sels de bases azotées (éthanolamine, triméthylamine, méthylamine, benzylamine, N-benzyl-β-phé- néthylamine, choline, arginine, leucine, lysine, N-méthyl glucamine).As examples of pharmaceutically acceptable salts, there may be mentioned addition salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis-β- oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl-β-phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
Parmi les composés de formule (I) sont préférés les composés suivants :Among the compounds of formula (I), the following compounds are preferred:
8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-eJ pyrazine-4-one, 8-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-méthyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-chloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-phényl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-eJ pyrazine-4-one, 8-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2 -e] pyrazine-4-one, 9-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one, 8-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9 -chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-phenyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-4-one,
8-(1-imidazolyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 4-oxo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-sulfonique, 7-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-bromo-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-fluoro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 6,7-dichloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,8-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8,9-dichloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,9-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro 9-bromo-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-8-méthoxy-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-amino-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-(3-phényluréido)-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-acétamido-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-8-diméthylaminométhylèneamino-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,8- (1-imidazolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 4-oxo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-sulfonic, 7-methyl-5H, 10H-imidazo [1, 2-a] indeno [1 , 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-bromo-5H, 10H-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-4-one, 9-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 6.7 -dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7,8-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1 , 2-e] pyrazine-4-one, 8,9-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7,9-dichloro-5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro 9-bromo-5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 5H, 10H-8-methoxy-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-amino-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8- (3-phenylureido) -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5H, 10H-8-acetamido-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-dimethylaminomethyleneamino-imidazo [1, 2-a] indeno [ 1, 2-e] pyrazine-4-o born,
7-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxy-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-acétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,7-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxy-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(E-diméthylaminométhylène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,10- (E-dimethylaminomethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-hydroxyméthylène-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-hydroxymethylene-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10J0-diméthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10:1'-cyclopropane]-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10:1'-cyclopentane]-4-one, 10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxyméthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-furylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 10-(4-pyridylméthylène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(phénylpropyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-pyridylméthylène)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-pyridylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyridylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-imidazolylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide (4-oxo-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)amino- oxyacétique, 10-propionamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyramido-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 10-amino-7-chloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzènesulfonylamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10J0-dimethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-10: 1'-cyclopropane] -4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10: 1'-cyclopentane] -4- one, 10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxymethyl-5H, 10H-imidazo [1, 2-a] indeno [ 1, 2-e] pyrazine-4-one, 10- (2-furylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 10- (4 -pyridylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (phenylpropyl) -5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 10- (3-pyridylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-imidazolylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-isobutyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid (4-oxo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-ylidene) amino-oxyacetic, 10-propionamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- amino-8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-methyluréido) -5H, 10H-imidazo [1, 2- a] indeno [1,2-e] pyrazine-4-one, 10-isobutyramido-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 10-amino- 7-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-benzenesulfonylamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyrazinylméthylène)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-(2-pyrazinylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-méthylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-méthyl-10-(4-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 10-(4-pipéridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzyl-7-chloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4, 10-dione, 10-(3-phényluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-(3-phényluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-méthyl-10-[2-(pyridine-4-yl)éthyl]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one,10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-pyrazinylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10- (2-pyrazinylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-10-methylamino-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 10-methyl-10- (4-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one, 10- (4-piperidylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-benzyl-7-chloro-5H, 10H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4, 10-dione, 10- (3-phenylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-10- (3-phenylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-methyl-10- [2- (pyridine-4-yl) ethyl] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
9-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]ρyrazine-4-one, 8-éthoxycarbonylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-cyanophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,9-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] ρyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-cyanophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 8-phénylacétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-tert-butyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one, 8-phenylacetamido-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4 -one, 8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-benzylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-tert-butyluréido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e ] pyrazine-4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-benzamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(4-phénylbutyrylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(5-phénylvalérylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-éthoxycarbonylméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (4-phenylbutyrylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (5-phenylvalerylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3 -ethoxycarbonylmethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-carboxyméthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (3-carboxymethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(3,3-diméthyluréido)-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-hydroxy-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-aminopropionamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-aminoacétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-nitrophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(2-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 8-[3-(2-nitrophényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4- one,8- (3,3-dimethylureido) -5HJOH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-hydroxy-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-aminopropionamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-aminoacetamido -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-nitrophenyl) ureido] -5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (2-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine - 4-one, 8- [3- (2-nitrophenyl) ureido] -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one,
8-[3-(4-aminophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- [3- (4-aminophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-methoxyphenyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
8-(4-méthylpentanoyl)amino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4 one,
N,N-diméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- sulfonamide,N, N-dimethyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-sulfonamide,
8-(3-phénylthiouréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-phenylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-méthylthiouréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(2-oxo-1 -imidazolinyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (2-oxo-1 -imidazolinyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-formamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-éthoxycarbonylpropionylamino)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-ethoxycarbonylpropionylamino) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-éthoxycarbonyléthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- [3- (2-ethoxycarbonylethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-carboxyéthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-carboxyethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(2-fluorophényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (2-fluorophenyl) ureido ] -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one,
8-(3-éthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,8- (3-ethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-morpholino-uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3-morpholino-ureido] -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-hydroxyimino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e] pyrazine-4-one,10-amino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4, 10-dione,8- (3-methylureido) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4, 10-dione,
8-[3-(3-aminophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one-8-carboxylique,8- [3- (3-aminophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5H acid, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one-8-carboxylic,
8-uréido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-ureido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-aminoéthyl)thiouréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-thiouréido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3- (2-aminoethyl) thiouréido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8-thiouréido-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-imidazoline-2-yl)amino]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8 - [(2-imidazoline-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[(1-pyrrolidinyl)carbonylamino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazi- ne-4-one, 8-[(1-azétidinyl)carbonylamino]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazi-ne-8 - [(1-pyrrolidinyl) carbonylamino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8 - [(1-azetidinyl) carbonylamino] - 5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazi-ne-
4-one,4-one,
8-(3-propyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-propylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-isopropyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-isopropylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-butyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[(2-thiazolin-2-yl)amino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (3-butylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8 - [(2-thiazolin-2-yl) amino] -5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(1 ,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (1, 3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-carbométhoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one, 8-[3-(3-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carbomethoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-carboxyphenyl ) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carbométhoxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one, 8-[3-(4-carboxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carbomethoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (4-carboxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(3-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (3-fluorobenzyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-fluorobenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 9-carboxy-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-carboxamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3- (4-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 9-carboxy-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-diéthylcarboxamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-(N-éthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(4-méthoxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,9- (N-diethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-methoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one,
8-méthylsulfonamido-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one-10-carboxylate d'éthyle, 10-imino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-carboxybenzyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-carboxybenzylidène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8-methylsulfonamido-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-4-one-10-carboxylate, 10-imino-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 10- (2-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1 , 2-e] pyrazine-4-one, 10- (3-carboxybenzylidene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-(3-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-[(1 -méthylimidazol-2-yl)méthylène]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10- (3-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-aminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10 - [(1 -methylimidazol-2-yl) methylene] -5H, 10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-4-one,
10-(carboxyméthyl)-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 10-(carboxyméthylène)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 5-(4-hydroxy-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)penta- noïque, 10-(1 -carboxy- 1-hydroxyméthyl)-8-(3-méthyluréido)-5H,10H-imidazo[1 , 2- a]indéno[1 ,2-e]pyrazine-4-one,10- (carboxymethyl) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 10- (carboxymethylene) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 5- (4-hydroxy-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-ylidene) pentanoic acid, 10- (1 -carboxy- 1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one,
10-nicotinoylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-nicotinoylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
3-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)amino- carbonyl]propionate de méthyle,3- [10- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionate,
10-(3-diéthylaminopropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,10- (3-diethylaminopropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-formamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
(10R)-10[(R)-α-méthoxy-α-trifluorométhylphénylacétamido]-5H,10H-imida- zo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,(10R) -10 [(R) -α-methoxy-α-trifluoromethylphenylacetamido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
(10S)-10[(R)-α-méthoxy- -trifluorométhylphénylacétamido]-5H,10H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,(10S) -10 [(R) -α-methoxy- -trifluoromethylphenylacetamido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-phénylacétamido-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-phenylacetamido-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
N-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]carba- mate de tert-butyle,N- [10- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] tert-butyl carbamate,
10-(1-pyrrolyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (1-pyrrolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
1 -[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]pyrrole-2- carboxylate de méthyle,1 - [10- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] pyrrole-2-carboxylate,
10-méthoxyimino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-acétamido-10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-methoxyimino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-acetamido-10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-(4-imidazolylméthyl)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (4-imidazolylmethyl) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 10-(carboxyméthylène)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-n-propyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2- e]pyrazine-4-one,10-amino-10-methyl-8- (3-n-propylureido) -5H, 10H-imidazo [1,2-a] indeno [1,2- e] pyrazine-4-one,
10-(3-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-aminobenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-acétylaminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (3-aminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-aminobenzylidene) -5H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 10- (3-acetylaminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-méthoxycarbonylbenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- (3-methoxycarbonylbenzylidene) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
10-amino-10-(3-phénylpropyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 5-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-10-yl)valérique,10-amino-10- (3-phenylpropyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5- (10-methyl-4,5- dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl) valeric,
4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyrazine-10- yl)butyronitrile, acide 4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)butyrique,4- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyronitrile, acid 4- (10- methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyric,
10-hydroxyméthyl-10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide (10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)acétique,10-hydroxymethyl-10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, acid (10-methyl-4,5-dihydro-4-oxo- 10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) acetic,
3-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- yl)propionitrile, acide 3-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)propionique, 10-méthyl-10-[(1-méthylimidazol-2-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno3- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl) propionitrile, acid 3- (10-methyl -4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) propionic, 10-methyl-10 - [(1- methylimidazol-2-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-4-one,[1, 2-e] pyrazine-4-one,
10-[(1 -méthylimidazol-5-yl)méthylène]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10 - [(1-methylimidazol-5-yl) methylene] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-[(1-méthylimidazol-5-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyra- zine-4-one,10 - [(1-methylimidazol-5-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-[3-(3-fluorophényl)uréido]-10-(carboxyméthyl)-5H,10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno8- [3- (3-fluorophenyl) ureido] -10- (carboxymethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid [8 - (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (+) [8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3-methyluréido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-10-yl]acétique, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-yl)gly- colique,[1, 2-e] pyrazine-10-yl] acetic, acid (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl ) glycolic,
10-méthyl-10-(1 -pyrrolyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 1 -[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)] pyrrole-2-carboxylique, acide 3-[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyl]propionique,10-methyl-10- (1 -pyrrolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid 1 - [10- (4-oxo-4 , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] pyrrole-2-carboxylic acid 3- [10- (4-oxo-4,5-dihydro-10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
10-amino-10-éthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-ethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-benzyl-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-benzyl-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-propyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]propionique,10-amino-10-propyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 3- [10- (10-methyl-4-oxo-4-acid) , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
N-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zinyl)]carbamate de tert-butyle, acide 4-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]butyrique,N- [10- (10-methyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] tert-butyl carbamate, acid 4- [10- (10-methyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] butyric,
10-amino-10-isopropyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-isopropyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-butyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-butyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-méthyl-10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one et ses énantiomères,10-methyl-10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-amino-10-methyl-8- (3-methylureido) - 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one and its enantiomers,
10-(1 ,3-diméthyl-1H-pyrazole-4-méthylène)-5H,10H-imidazo[1,2-a]indéno10- (1, 3-dimethyl-1H-pyrazole-4-methylene) -5H, 10H-imidazo [1,2-a] indeno
[1 ,2-e]pyrazine-4-one, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imidazo [1 ,2-a]indéno[1 ,2-e]pyrazinyl]aminocarbonyl}propionique, (10'RS)-spiro[pyrrolidine-3,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,[1, 2-e] pyrazine-4-one, 3- {10- [10-methyl-8- (3-methylureido) -4-oxo-4,5-dihydro-1 OH-imidazo acid [1, 2 -a] indeno [1, 2-e] pyrazinyl] aminocarbonyl} propionic, (10'RS) -spiro [pyrrolidine-3,10'-5'H, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one,
(10'RS)-spiro[pipéridine-2,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-(10'RS) -spiro [piperidine-2,10'-5'H, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -
4'-one, (10'RS)-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,4'-one, (10'RS) -spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-méthyl-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-methyl-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1,2-a] indéno [1, 2-e] pyrazine] -4'-one,
(+)-1-méthyl-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1,2-e]py- razine]-4'-one,(+) - 1-methyl-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1,2-e] py- razine] -4'-one,
(-)-1-méthyl-spiro[pyrrolidine-2,10'-5Η,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine]-4'-one, acide (10,RS)-4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pyrrolidine-2,10'-10Η-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1-yl]}-butyrique, spiro[pipéridine-4J0'-5Η,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one, acide 4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pipéridine-4,10'-10Η-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-1 -yl]}butyrique,(-) - 1-methyl-spiro [pyrrolidine-2,10'-5Η, 10'H-imidazo [1, 2-a] indeno [1, 2-e] py- razine] -4'-one, acid (10 , RS) -4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [pyrrolidine-2,10'-10Η-imidazo [1, 2-a] indéno [1 , 2-e] pyrazine-1-yl]} - butyric, spiro [piperidine-4J0'-5Η, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'- one, 4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [piperidine-4,10'-10Η-imidazo [1, 2- a] indeno [1, 2-e] acid pyrazine-1 -yl]} butyric,
1-phénylacétyl-spiro[pipéridine-4J0'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one, 1-(méthylcarbamoyl)-spiro[pipéridine-4,10'-5'H,10Η-imidazo[1 ,2-a]indéno1-phenylacetyl-spiro [piperidine-4J0'-5Η, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, 1- (methylcarbamoyl) -spiro [piperidine-4 , 10'-5'H, 10Η-imidazo [1, 2-a] indéno
[1 ,2-e]pyrazine]-4'-one,[1, 2-e] pyrazine] -4'-one,
1-méthyl-spiro[pipéridine-4,10'-5Η,10'H-imidazo[1,2-a]indéno[1,2-e]pyra- zine]-4'-one,1-methyl-spiro [piperidine-4,10'-5Η, 10'H-imidazo [1,2-a] indeno [1,2-e] pyrazine] -4'-one,
1-benzyl-spiro[pipéridine-4,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,1-benzyl-spiro [piperidine-4,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
1-phénéthyl-spiro[pipéridine-4,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,1-phenethyl-spiro [piperidine-4,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-acétyl-spiro[pyrrolidine-2,10'-5'H,10'H-imidazo[1,2-a]indéno[1 ,2-e] pyrazine]-4'-one, (10'RS)-1-[(3-méthyluréido)acétyl]-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo(10'RS) -1-acetyl-spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1,2-a] indeno [1, 2-e] pyrazine] -4'-one , (10'RS) -1 - [(3-methylureido) acetyl] -spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one,[1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-(phénylcarbamoyl)-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine]-4'-one, (10ΗS)-1-méthyl-8,-fluoro-spiro[pyrrolidine-2 0,-5ΗI10Η-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1- (phenylcarbamoyl) -spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, ( 10ΗS) -1-methyl-8 , -fluoro-spiro [pyrrolidine-2 0 , -5Η I 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-éthyl-spiro[pyrrolidine-2,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-ethyl-spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one ,
(10'RS)-1-propyl-spiro[pyrrolidine-2,10'-5Η,10'H-imidazo [1,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-propyl-spiro [pyrrolidine-2,10'-5Η, 10'H-imidazo [1,2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pyrrolidine-2,10'-10'H-imidazo(10'RS) -4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [pyrrolidine-2,10'-10'H-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique,[1, 2-a] indeno [1, 2-e] pyrazine-1 -yl]} - butyric,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylate d'éthyle, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxamide,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxamide,
8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylate d'éthyle, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, 7-chloro-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxylate d'éthyle, acide 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide 10-(1 -pyrrolyle)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl azazine-2-carboxylate, acid 8- (3-methyluréido) -4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 7-chloro-4,5-dihydro -4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 4,5-dihydro-4-oxo-10H-imidazo acid [ 1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 10- (1 -pyrrolyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a ] indeno [1, 2-e] pyrazine-2-carboxylic, 10-amino-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
2-carboxylique, acide 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylique, acide 7-chloro-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 8-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 5-(2-carboxy-10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indéno2-carboxylic, 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 7-chloro-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-amino-4,5-dihydro- acid 4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 5- (2-carboxy-10-methyl-4,5-dihydro-4-oxo- 10H-imidazo [1,2-a] indeno
[1 ,2-e]pyrazine-10-yl)valérique, acide 4,5-dihydro-4, 10-dioxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide (E)-4,5-dihydro-4-oxo-10-(3-carboxybenzylidène)-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 10-(3-carboxypropionylamino)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 10-(3-phényluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-[(1 -méthylimidazol-2-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1 -méthylimidazol-2-yl)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 4-[10-(2-carboxy-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zinylidène)aminooxy]butyrique, 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxyl ate d'éthyle, acide 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 4-oxo-10-[1 -(2-oxo-2,5-dihydropyrrolyl)]-4,5-dihydro-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, et leurs sels pharmaceutiquement acceptables ainsi que leurs énantiomères lorsqu'ils comportent un carbone asymétrique.[1, 2-e] pyrazine-10-yl) valeric, 4,5-dihydro-4, 10-dioxo-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxy- lique, acid (E) -4,5-dihydro-4-oxo-10- (3-carboxybenzylidene) -imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic acid 10- (3-carboxypropionylamino) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic acid 10- (3- phenylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-2-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1,2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-5-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1 -methylimidazol-2-yl) methyl] -4 , 5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-5-yl) methyl] -4 , 5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 4- [10- (2-carboxy-4,5-dihydro- 4-oxo-imidazo [1, 2-a] indie no [1, 2-e] pyrazinylidene) aminooxy] butyric, 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- Ethyl 2-carboxyl ate, 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic acid 4-oxo-10- [1 - (2-oxo-2,5-dihydropyrrolyl)] - 4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic, and their pharmaceutically acceptable salts as well as their enantiomers when they contain an asymmetric carbon.
Ces composés sont décrits dans les brevets EP662971 , EP708774, EP752991 , EP752992, EP772615, EP789699.These compounds are described in patents EP662971, EP708774, EP752991, EP752992, EP772615, EP789699.
2 - des dérivés de 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one de formule :2 - 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one derivatives of formula:
dans laquelle,in which,
- R' représente un atome d'hydrogène ou un radical carboxy, alcoxycarbo- nyle, -CO-NR'4R'5, -PO3H2 ou -CH2OH,- R 'represents a hydrogen atom or a carboxy, alkoxycarbonyl, -CO-NR'4R'5, -PO3H2 or -CH2OH radical,
- R'-| représente un radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR'5R'g ou -CO-NH-R'7,- R'- | represents a radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR ' 5 R'g or -CO-NH-R' 7 ,
- R'3 représente un radical alkyle, phényle, phénylalkyle, cycloalkyle ou -NR'gR's,- R'3 represents an alkyl, phenyl, phenylalkyl, cycloalkyl or -NR'gR's radical,
- R'4 représente un atome d'hydrogène ou un radical alkyle,- R'4 represents a hydrogen atom or an alkyl radical,
- R'5 représente un atome d'hydrogène ou un radical alkyle, phényle, cycloalkyle ou phénylalkyle,R'5 represents a hydrogen atom or an alkyl, phenyl, cycloalkyl or phenylalkyl radical,
- R'g représente un atome d'hydrogène ou un radical alkyle, ou bien R'5 et R'g forment avec l'atome d'azote auquel ils sont rattachés un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 6 atomes de carbone et éventuellement un ou plusieurs autres hétéroatomes choisis parmi O, S, N,- R'g represents a hydrogen atom or an alkyl radical, or else R'5 and R'g form, with the nitrogen atom to which they are attached, a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 6 carbon atoms and optionally one or more other heteroatoms chosen from O, S, N ,
- R'7 représente un radical phényle, phénylalkyle ou -alk-COOR'4,- R'7 represents a phenyl, phenylalkyl or -alk-COOR'4 radical,
- R'g représente un atome d'hydrogène ou un radical alkyle, cycloalkyle ou phénylalkyle,R'g represents a hydrogen atom or an alkyl, cycloalkyl or phenylalkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
leurs énantiomères et stéréoisomères et leurs sels pharmaceutiquement ac- ceptables.their enantiomers and stereoisomers and their pharmaceutically acceptable salts.
Sauf mention contraire, dans les définitions qui précédent, les radicaux et portions alcoxy, alkyle et alkylène contiennent 1 à 6 atomes de carbone et sont en chaîne droite ou ramifiée et les radicaux cycloalkyle contiennent 3 à 6 atomes de carbone.Unless otherwise stated, in the definitions above, the alkoxy, alkyl and alkylene radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain and the cycloalkyl radicals contain 3 to 6 carbon atoms.
De préférence, lorsque R'5 et R'g forment avec l'atome d'azote auquel ils sont rattachés un hétérocycle celui-ci est choisi parmi les cycles azétidine, pyrrolidine, pipéridine, pipérazine et morpholine.Preferably, when R′5 and R′g form with the nitrogen atom to which they are attached a heterocycle, the latter is chosen from the azetidine, pyrrolidine, piperidine, piperazine and morpholine rings.
De préférence, le substituant R'-| est en position -8 ou -9.Preferably, the substituent R'- | is in position -8 or -9.
Les composés de formule (la) comportant un reste basique peuvent être éventuellement transformés en sels d'addition avec un acide minéral ou organique.The compounds of formula (la) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
Les composés de formule (la) comportant un reste acide peuvent éventuellement être transformés en sels métalliques ou en sels d'addition avec les bases azotées. Comme exemples de sels pharmaceutiquement acceptables, peuvent être cités les sels d'addition avec les acides minéraux ou organiques (tels que acétate, propionate, succinate, benzoate, fumarate, maléate, oxalate, mé- thanesulfonate, iséthionate, théophyllinacétate, salicylate, méthylène-bis-β- oxynaphtoate, chlorhydrate, sulfate, nitrate et phosphate), les sels avec les métaux alcalins (sodium, potassium, lithium) ou avec les métaux alcalinoter- reux (calcium, magnésium), le sel d'ammonium, les sels de bases azotées (éthanolamine, triméthylamine, méthylamine, benzylamine, N-benzyl-β-phé- néthylamine, choline, arginine, leucine, lysine, N-méthyl glucamine).The compounds of formula (la) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases. As examples of pharmaceutically acceptable salts, there may be mentioned addition salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis-β- oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl-β-phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
Les composés préférés de formule (la) sont les suivants :The preferred compounds of formula (la) are the following:
acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)acé- tique,(4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-9-yl) acetic acid,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide, N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)mé- thyl]acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide, N - [(4,5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] acetamide,
9-[(3-méthyluréido)méthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,9 - [(3-methylureido) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, 8-(3-méthyluréido)méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,N-methyl- [4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4 acid, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) carboxamide, N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)carbonyl] glycine,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carboxamide, N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carbonyl] glycine,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno [1 ,2-e]pyrazine-2-carboxylique,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, acid 8- (N-ethylaminocarbonylmethyl) - 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno [1 ,2- e] pyrazine-2-carboxylique, acide 8-(2-carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 9-[(3-méthyluréido)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-N-méthylaminocarbonylméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno-no [1, 2-e] ethyl pyrazine-2-carboxylate, acid 9- N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-2-carboxylic, 8- (2-carboxyethyl) acid -4.5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9 - [(3-methylureido) methyl] -4,5-dihydro-4 -oxo-10H-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic, 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 9-N-methylaminocarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-2-carboxylic acid 9- (1 -carboxyethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic,
leurs sels, leurs énantiomères et diastéréoisomères.their salts, enantiomers and diastereoisomers.
Ces dérivés sont décrits dans le brevet EP820455.These derivatives are described in patent EP820455.
3 - des dérivés de 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one de formule : 3 - 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one derivatives of formula:
dans laquellein which
R" représente un atome d'hydrogène ou un radical -COOH, -alk-COOH, -PO3H2, -CH2-PO3H2, -CH=CH-COOH ou phényle substitué par un radical carboxy,R "represents a hydrogen atom or a radical -COOH, -alk-COOH, -PO3H2, -CH2-PO3H2, -CH = CH-COOH or phenyl substituted by a carboxy radical,
R"1 représente un radical -alk-CN, -alk-COOH, -alk-Het", -alk-P03H2 ou -alk-C0-NH-S02R"2,R "1 represents a radical -alk-CN, -alk-COOH, -alk-Het", -alk-P03H2 or -alk-C0-NH-S02R "2,
R"2 représente un radical alkyle ou phényle,R "2 represents an alkyl or phenyl radical,
alk représente un radical alkyle,alk represents an alkyl radical,
Het" représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes choisis parmi O, S, N, l'hétérocycle étant éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle,Het "represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms chosen from O, S, N, the heterocycle being optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
les isomères (E et Z) des composés pour lesquels R représente un radical -CH=CH-COOH, les racémiques, énantiomères et diastéréoisomères des composés pour lesquels R représente un radical -alk-COOH et/ou R, représente un radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H2 ou -alk-C0-NH-S02R2the isomers (E and Z) of the compounds for which R represents a radical -CH = CH-COOH, the racemates, enantiomers and diastereoisomers of the compounds for which R represents a radical -alk-COOH and / or R represents a radical -alk -CN, -alk-COOH, -alk-Het, -alk-P03H2 or -alk-C0-NH-S02R2
et leurs sels pharmaceutiquement acceptables. Sauf mention contraire, dans les définitions qui précédent les radicaux alkyle et alcoxy contiennent 1 à 6 atomes de carbone en chaîne droite ou ramifiée.and their pharmaceutically acceptable salts. Unless otherwise stated, in the definitions preceding the alkyl and alkoxy radicals contain 1 to 6 carbon atoms in a straight or branched chain.
De préférence, le substituant R"1 est en position -8 ou -9.Preferably, the substituent R "1 is in position -8 or -9.
De préférence, Het représente un cycle tétrazole-5-yle.Preferably, Het represents a tetrazole-5-yl ring.
Les composés de formule (Ib) comportant un reste basique peuvent être éventuellement transformés en sels d'addition avec un acide minéral ou organique.The compounds of formula (Ib) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
Les composés de formule (Ib) comportant un reste acide peuvent éventuellement être transformés en sels métalliques ou en sels d'addition avec les ba- ses azotées.The compounds of formula (Ib) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
Comme exemples de sels pharmaceutiquement acceptables, peuvent être cités les sels d'addition avec les acides minéraux ou organiques (tels que acétate, propionate, succinate, benzoate, fumarate, maléate, oxalate, mé- thanesulfonate, iséthionate, théophyllinacétate, salicylate, méthylène-bis-β- oxynaphtoate, chlorhydrate, sulfate, nitrate et phosphate), les sels avec les métaux alcalins (sodium, potassium, lithium) ou avec les métaux alcalinoter- reux (calcium, magnésium), le sel d'ammonium, les sels de bases azotées (éthanolamine, triméthylamine, méthylamine, benzylamine, N-benzyl-β-phé- néthylamine, choline, arginine, leucine, lysine, N-méthyl glucamine).As examples of pharmaceutically acceptable salts, there may be mentioned addition salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis-β- oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl-β-phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
Parmi les composés de formule (Ib) sont préférés les composés suivants :Among the compounds of formula (Ib) the following compounds are preferred:
9-(1 H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-phosphonique, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique,9- (1 H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, acid 9- (1 H-tetrazole- 5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9- (1 H- tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic,
9-cyanométhyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 9-(4-phényl-1 H-imidazol-2-yl-méthyl)-4,5-dihydro-4-oxo-10H-imida- zo[1 ,2-a]indéno [1 ,2-e]pyrazine-2-carboxylique, acide 3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (£)-3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 9-benzènesulfonamidocarbonylméthyl-4-oxo-4,5-dihydro-10H-imidazo [1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-méthylsulfonamido-carbonylméthyl-4-oxo-4,5-dihydro-10H-imidazo9-cyanomethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4-oxo-4,5-dihydro-10H-imidazo acid [1 , 2-a] indeno [1, 2-e] pyrazine-2-methylphosphonic acid 9- (4-phenyl-1 H-imidazol-2-yl-methyl) -4,5-dihydro-4-oxo -10H-imida- zo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2 -a] indeno [1, 2-e] pyrazin-2-yl) -propionic, acid (£) -3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-yl) -acrylic, 4-oxo-9-phosphonomethyl-5,10-dihydro-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazin-2-carboxylic acid 2- (4-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic , 2- (3-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-acetic acid, 2- (2- carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 9-benzenesulfonamidocarbonylmethyl-4-oxo-4,5- dihydro-10H-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-2-carboxylic, 9-methylsulfonamido-carbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique, leurs sels pharmaceutiquement acceptables et leurs énantiomères losqu'ils comportent un carbone asymétrique.[1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
Ces composés sont décrits dans le brevet EP880522.These compounds are described in patent EP880522.
4 - des dérivés de pyrazine-2,3-dione de formule : 4 - pyrazine-2,3-dione derivatives of formula:
dans laquellein which
- R"' représente un radical C(R"'4)R'"5, CH-R"'g ou C=R'"7,- R "'represents a radical C (R"' 4) R '" 5 , CH-R"' g or C = R '" 7 ,
- R"'-| et R'"2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux amino, nitro ou -NH-CO-NR"'-| -| R"'i2> - R "'- | and R'" 2, identical or different, represent hydrogen or halogen atoms or amino, nitro or -NH-CO-NR "" - | - | R "'i2 >
- R'"3 représente un atome d'oxygène,- R '"3 represents an oxygen atom,
- R'"4 représente un radical alkyle,- R '"4 represents an alkyl radical,
- R'"5 représente un radical -alk-COOR'"-|Q,- R '"5 represents a radical -alk-COOR'" - | Q,
- R"'g représente un atome d'hydrogène ou un radical -NR"'-|4R"'-|5,- R "'g represents a hydrogen atom or a radical -NR"' - | 4R "'- | 5,
- R'"7 représente un radical NOH ou C(COOR"'-|o)R"'2θ,- R '"7 represents a NOH or C (COOR"' - | o) R "'2θ radical,
- R"'-|o représente un atome d'hydrogène ou un radical alkyle,- R "'- | o represents a hydrogen atom or an alkyl radical,
- R"'-| -| représente phényle,- R "'- | - | represents phenyl,
- R"'i2 représente un atome d'hydrogène,- R "'i2 represents a hydrogen atom,
- R"'-|4 représente un atome d'hydrogène,- R "'- | 4 represents a hydrogen atom,
- R"'i5 représente un atome d'hydrogène ou un radical -COR'"22.- R "'i5 represents a hydrogen atom or a radical -COR'" 22.
- R'"20 représente un atome d'hydrogène,- R '"20 represents a hydrogen atom,
- R'"22 représente un radical alkyle, - alk représente un radical alkyle,- R '"22 represents an alkyl radical, - alk represents an alkyl radical,
les isomères (E et Z) des composés pour lesquels R"' représente un radical C=R*"7 et R'"7 représente un radical C(COOR"'-|o)R"'2θ, 'es énantiomères et diastéréoisomères des composés de formule (I) pour lesquels R représente un radical C(R4)Rs ou CH-Rg,the isomers (E and Z) of the compounds for which R "'represents a radical C = R * " 7 and R'"7 represents a radical C (COOR"'- | o) R "' 2θ, 'es enantiomers and diastereoisomers compounds of formula (I) for which R represents a radical C (R4) Rs or CH-Rg,
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
Dans les définitions qui précédent, les radicaux et portions alkyle contiennent 1 à 6 atomes de carbone et sont en chaîne droite ou ramifiée et les atomes d'halogène sont choisis parmi le fluor, le chlore, le brome et l'iode.In the definitions above, the alkyl radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain and the halogen atoms are chosen from fluorine, chlorine, bromine and iodine.
Les composés de formule (le) comportant un reste basique peuvent être éventuellement transformés en sels d'addition avec un acide minéral ou organique.The compounds of formula (Ie) comprising a basic residue can optionally be converted into addition salts with a mineral or organic acid.
Les composés de formule (le) comportant un reste acide peuvent éventuellement être transformés en sels métalliques ou en sels d'addition avec les bases azotées.The compounds of formula (Ic) comprising an acid residue can optionally be converted into metal salts or into addition salts with nitrogenous bases.
Comme exemples de sels pharmaceutiquement acceptables, peuvent être cités les sels d'addition avec les acides minéraux ou organiques (tels que acétate, propionate, succinate, benzoate, fumarate, maléate, oxalate, mé- thanesulfonate, iséthionate, théophyllinacétate, salicylate, méthylène-bis-β- oxynaphtoate, chlorhydrate, sulfate, nitrate et phosphate), les sels avec les métaux alcalins (sodium, potassium, lithium) ou avec les métaux alcalinoter- reux (calcium, magnésium), le sel d'ammonium, les sels de bases azotées (éthanolamine, triméthylamine, méthylamine, benzylamine, N-benzyl-β-phé- néthylamine, choline, arginine, leucine, lysine, N-méthyl glucamine).As examples of pharmaceutically acceptable salts, there may be mentioned addition salts with mineral or organic acids (such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulfonate, isethionate, theophyllinacetate, salicylate, methylene- bis-β- oxynaphthoate, hydrochloride, sulphate, nitrate and phosphate), salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (calcium, magnesium), ammonium salt, salts of nitrogen bases (ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl-β-phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine).
Parmi les composés de formule (le) sont préférés les composés suivants : 1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione, 8-chloro-1 ,4-dihydro-5H-indeno[1 ,2-b]pyrazine-2,3-dione, acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5-yl)acéti- que,Among the compounds of formula (Ic), the following compounds are preferred: 1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, 8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, acid (5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-5-yl) acetic,
5-amino-8-chloro-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione, 7-(3-phényluréido)-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,5-amino-8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, 7- (3-phenylureido) -1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-2,3-dione,
(E)-5-carboxyméthylène-8-chloro-1 ,4-dihydro-indéno[1 ,2-b]pyrazine-2,3- dione, acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5- yl)acétique, (+) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1 H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(E) -5-carboxymethylene-8-chloro-1,4-dihydro-indeno [1,2-b] pyrazine-2,3-dione, acid (8-chloro-5-methyl-2,3-dioxo- 1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-5-yl) acetic, (+) acid (5-methyl-2,3-dioxo-1, 4-dihydro-1 H-indeno [ 1, 2-b] pyrazine-5-yl) acetic,
(-) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1 H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(-) (5-methyl-2,3-dioxo-1, 4-dihydro-1 H-indeno [1, 2-b] pyrazine-5-yl) acetic acid,
(+) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine- 5-yl)acétique,(+) (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-5-yl) acetic acid,
(-) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-(-) acid (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indéno [1, 2-b] pyrazine-
5-yl)acétique5-yl) acetic
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
Ces composés sont décrits dans le brevet EP752988.These compounds are described in patent EP752988.
5 - des dérivés de quinoxalinedione tels que ceux décrits dans les brevets W09838186, WO9749701 , W09719366, W09746555, W09732873, WO9637500, W09628445, W09617832, W09612725, W09612724, WO9608485, W09535289, W09425469, WO9306103, WO9207847, JP08003159, EP260467, EP283959, US4975430, DE4314592,5 - quinoxalinedione derivatives such as those described in the patents W09838186, WO9749701, W09719366, W09746555, W09732873, WO9637500, W09628445, W09617832, W09612725, W09612724, WO9608485, W9958485, W09356289, W095359, , DE4314592,
et plus particulièrement les composés suivants : acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1 (2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775), 1 ,4-dihydro-6-(1 H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione (YM 900 et YM90K), acide 3,4-dihydro-7-(1 H-imidazol-1 -yl)-6-nitro-2,3-dioxo-1 (2H)-quinoxaline- acétique (YM 872), 1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX),and more particularly the following compounds: [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -quino-noxalinyl] methyl] phosphonic acid (ZK200775 ), 1,4-dihydro-6- (1 H-imidazol-1-yl) -7-nitro-2,3-quinoxalinedione (YM 900 and YM90K), 3,4-dihydro-7- acid (1 H-imidazol- 1-yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic (YM 872), 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo [ f] quinoxaline-7-sulfonamide (NBQX),
1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX) 1 ,2,3,4-tétrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX)1, 4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX) 1,2,3,4-tetrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX)
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
6 - des dérivés de quinoxaline tels que ceux décrits dans les brevets WO9827097, W09817672, W09732858, WO9708155, JP8059660, W09426746, W09421639, WO9608495, WO9308173, EP511152, EP676397, DE4314593,6 - quinoxaline derivatives such as those described in patents WO9827097, W09817672, W09732858, WO9708155, JP8059660, W09426746, W09421639, WO9608495, WO9308173, EP511152, EP676397, DE4314593,
7 - des dérivés de quinoxalinone tels que ceux décrits dans les brevets WO9608493, WO9608492, W09521842,7 - quinoxalinone derivatives such as those described in patents WO9608493, WO9608492, W09521842,
8 - des dérivés de benzodiazépine tels que ceux décrits dans les brevets HU9700688, W09734878, GB231 1779, DE4428835, WO9606606, EP492485, FR25682528 - benzodiazepine derivatives such as those described in patents HU9700688, W09734878, GB231 1779, DE4428835, WO9606606, EP492485, FR2568252
et plus particulièrement les composés suivants : 1 -(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4- di- hydro-5H-2,3-benzodiazépine (LY 300168),and more particularly the following compounds: 1 - (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
4-(8-méthyl-9H-1 ,3-dioxolo[4,5-h][2,3]benzodiazépin-5-yl-benzénamine4- (8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepin-5-yl-benzenamine
(GYKI52466),(GYKI52466),
(-)-3-Acétyl-1 -(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H- 2,3-benzodiazépine (LY 300164),(-) - 3-Acetyl-1 - (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-2,3-benzodiazepine (LY 300164),
et leurs sels pharmaceutiquement acceptables. 9 - des dérivés de benzothiadiazepine tels que ceux décrits dans le brevet EP692484,and their pharmaceutically acceptable salts. 9 - benzothiadiazepine derivatives such as those described in patent EP692484,
10 - des dérivés de benzofurane tels que ceux décrits dans le brevet WO9835950,10 - benzofuran derivatives such as those described in patent WO9835950,
11 - des dérivés de quinazolinone tels que ceux décrits dans les brevets W09838187, W09743276, et dans l'article paru dans J. Neurochem., 1998, 71 (1), 418-42611 - quinazolinone derivatives such as those described in patents W09838187, W09743276, and in the article published in J. Neurochem., 1998, 71 (1), 418-426
et plus particulièrement le produit connu sous le code Ro48-8587and more particularly the product known under the code Ro48-8587
12 - les dérivés de quinazolinedione tels que ceux décrits dans le brevet W09519346,12 - quinazolinedione derivatives such as those described in patent WO9519346,
13 - des dérivés de benzothiadiazide tels que ceux décrits dans le brevet W09812185,13 - benzothiadiazide derivatives such as those described in patent WO9812185,
14 - des dérivés d'isoquinoléine tels que ceux décrits dans le brevet US528495714 - isoquinoline derivatives such as those described in patent US5284957
et plus particulièrement les composés suivants :and more particularly the following compounds:
acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1 H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490)decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325), decahydro-6- [2- ( 1 H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic (LY 293558), decahydro-6- [2- (1 H-tetrazol-5-yl) acid ethyl] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490)
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
15 - des dérivés de quinolinone tels que ceux décrits dans le brevet EP640612 et plus particulièrement le composé suivant :15 - quinolinone derivatives such as those described in patent EP640612 and more particularly the following compound:
acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252) et ses sels pharmaceutiquement acceptables.(6,7-dichloro-1, 2-dihydro-2-oxo-3-qinolinyl) phosphonic acid (S176252) and its pharmaceutically acceptable salts.
16 - le composé connu sous le nom SH608.16 - the compound known as SH608.
De façon encore plus préférentielle, l'antagoniste des récepteurs AMPA est un antagoniste sélectif c'est-à-dire que ce composé est au moins 20 fois plus actif sur les récepteurs AMPA que sur les autres récepteurs du glutamate et, en particulier, le récepteur NMDA, et généralement 50 et même 100 fois plus actif.Even more preferably, the AMPA receptor antagonist is a selective antagonist, that is to say that this compound is at least 20 times more active on AMPA receptors than on other glutamate receptors and, in particular, the NMDA receptor, and generally 50 and even 100 times more active.
Parmi les antagonistes des récepteurs AMPA sélectifs, on peut citer les composés suivants :Among the selective AMPA receptor antagonists, the following compounds may be mentioned:
10-acétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxyméthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione, 9-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-éthoxycarbonylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxymethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-8-fluoro-5HJ0H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4,10-dione, 9-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- ( 3-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one,
8-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-benzamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(4-phénylbutyrylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5HJOH-imidazo [1, 2-a] indeno [ 1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3 -benzylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (4-phenylbutyrylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(5-phénylvalérylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (5-phenylvalerylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-8- (3,3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-
[3-(2-méthoxyphényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,[3- (2-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(4-méthylpentanoyl)amino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(3-méthylthiouréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-éthoxycarbonyléthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one,8- [3- (2-ethoxycarbonylethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-[3-(3-fluorophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(3-éthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,8- [3- (2-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (3-ethylureido) -5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10-amino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-hydroxyimino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one, 8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4J0-dione,10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 8- (3-methylureido) -5H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4J0-dione,
8-[3-morpholino-uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3-morpholino-ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-thiouréido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-thiouréido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-propyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-propylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-isopropyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-butyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-isopropylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-butylureido) -5H, 10H-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-thiazolin-2-yl)amino]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8 - [(2-thiazolin-2-yl) amino] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carbométhoxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one, 8-[3-(2-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carbomethoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (2-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorobenzyl)uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorobenzyl) ureido] -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-fluorobenzyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-carboxyphényl)uréido]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carboxyphenyl) ureido] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carboxybenzyl)uréido]-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carboxybenzyl) ureido] -5HJOH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(1 ,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (1, 3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-carboxamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9-carboxamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one,9- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
9-(N-éthylcarboxamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)acé- tique,9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetic,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)méthyl]a- cétamide,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] a-ketamide,
N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,N-methyl- [4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4 acid, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(3-méthyluréido)méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno [1 ,2-e]pyrazine-2-carboxylique, 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo- acid 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, acid 8- (N-ethylaminocarbonylmethyl) - 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4- oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,[1, 2-e] ethyl pyrazine-2-carboxylate, 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine -2-phosphonic, 9- (1 -carboxyethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid,
9-(1 H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-phosphonique,9- (1 H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, acid 9- (1 H-tetrazole- 5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9- (1 H- tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (£)-3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic, 9-carboxymethyl-4-oxo-4,5-dihydro acid -10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-methylphosphonic acid 3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [1,2 -a] indeno [1, 2-e] pyrazin-2-yl) -propionic, acid (£) -3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [1, 2- a] indeno [1, 2- e] pyrazine-2-yl) -acrylic, 4-oxo-9-phosphonomethyl-5, 10-dihydro-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazin-2-carboxylic acid 2- (4-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic , 2- (3-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic acid, 2- (2-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic acid,
10-(1-carboxy-1-hydroxyméthyl)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyl]propionique,10- (1-carboxy-1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, acid 3- [ 10- (4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
10-(carboxyméthylène)-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno [1 ,2- e]pyrazine-4-one,10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid [8- (3-methylureido ) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imidazo [1 ,2-a]indéno[1 ,2-e]pyrazinyl]aminocarbonyl}propionique, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide (lO'RSM-oxo^- -oxo^'.δ'-dihydro-spirotpyrrolidine^.lO'-IOΗ-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique, 1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (+) acid [8- ( 3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3 -methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, 3- {10- [10-methyl -8- (3-methyluréido) -4-oxo-4,5-dihydro-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl] aminocarbonyl} propionic acid 8- (3- methyluréido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid (lO'RSM-oxo ^ - -oxo ^ ' .δ'-dihydro-spirotpyrrolidine ^ .lO'-IOΗ-imidazo [1, 2-a] indéno [1, 2-e] pyrazine-1 -yl]} - butyric, 1, 2,3,4- tetrahydro-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide
(NBQX), acide décahydro-6-[2-(1 H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558),(NBQX), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558),
1 ,4-dihydro-6-(1H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione (YM 900 et YM90K), acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1(2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775), acide 3,4-dihydro-7-(1 H-imidazol-1 -yl)-6-nitro-2,3-dioxo-1 (2H)-quinoxaline- acétique (YM 872), 1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),1, 4-dihydro-6- (1H-imidazol-1-yl) -7-nitro-2,3-quinoxalinedione (YM 900 and YM90K), [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -qui- noxalinyl] methyl] phosphonic acid (ZK200775), acid 3,4- dihydro-7- (1 H-imidazol-1 -yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic (YM 872), 1, 4-dihydro-6,7-dinitro- 2,3-quinoxalinedione (DNQX),
1,2,3,4-tétrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX),1,2,3,4-tetrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX),
1-(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4- di- hydro-5H-2,3-benzodiazépine (LY 300168),1- (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
4-(8-méthyl-9H-1 ,3-dioxolo[4,5-h][2,3]benzodiazépin-5-yl-benzénamine (GYKI52466),4- (8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepin-5-yl-benzenamine (GYKI52466),
(-)-3-Acétyl-1-(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H-(-) - 3-Acetyl-1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-
2,3-benzodiazépine (LY 300164), acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1 H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490), acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le produit Ro48-8587, acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le produit SH6082,3-benzodiazepine (LY 300164), decahydro-6- [2- (1H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558), decahydro-6- [2- ( 1 H-tetrazol-5-yl) ethyl] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490), acid (6,7-dichloro-1, 2-dihydro-2-oxo- 3-qinolinyl) phosphonic (S176252), the product Ro48-8587, acid (6,7-dichloro-1, 2-dihydro-2-oxo-3-qinolinyl) phosphonic (S176252), the product SH608
leurs sels pharmaceutiquement acceptables et leurs énantiomères lorsqu'ils comportent un carbone asymétrique.their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
L'effet de l'association du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un antagoniste des récepteurs AMPA dans le traitement de la sclérose latérale amyotrophique a été déterminé chez des souris transgéniques qui constituent un modèle de la SLA selon le test suivant : des souris transgéniques (B6SJL-TgN(SOD1-G93A,G1H) hétérozygotes pour le gène muté codant pour un SOD1 pathologique trouvé dans certains cas de SLA sont partagées en 4 groupes A, B, C et D.The effect of the combination of riluzole or one of its pharmaceutically acceptable salts and an AMPA receptor antagonist in the treatment of amyotrophic lateral sclerosis was determined in transgenic mice which constitute a model of ALS according to the following test : transgenic mice (B6SJL-TgN (SOD1-G93A, G1H) heterozygous for the mutated gene coding for a pathological SOD1 found in certain cases of ALS are divided into 4 groups A, B, C and D.
Les animaux du groupe A sont des animaux de contrôle et ne reçoivent que 25 ml/kg de solution saline (0,9%) par voie sous-cutanée une fois par jour.The animals in group A are control animals and receive only 25 ml / kg of saline solution (0.9%) subcutaneously once a day.
Les animaux des groupes B sont traités à partir du 50 ème jour de vie avec 200 μg/ml de riluzole dans l'eau de boisson disponible ad libitum jusqu'à la mort (la consommation est de l'ordre de 3 à 3,5 ml/souris/jour).The animals of groups B are treated from the 50 th day of life with 200 μg / ml of riluzole in the drinking water available ad libitum until death (consumption is of the order of 3 to 3.5 ml / mouse / day).
Les animaux du groupe C sont traités à partir du 42 ème jour de vie avec 3 mg/kg/jour par voie sous-cutanée de l'antagoniste des récepteurs AMPA en solution saline jusqu'à la mort.The animals of group C are treated from the 42nd day of life with 3 mg / kg / day by the subcutaneous route of the AMPA receptor antagonist in saline solution until death.
Les animaux du groupe D sont traités à partir du 42 ème jour de vie avec 3 mg/kg/jour par voie sous-cutanée de l'antagoniste des récepteurs AMPA en solution saline et à partir du 50 ème jour de vie avec 200 μg/ml de riluzole dans l'eau de boisson jusqu'à la mort.The animals of group D are treated from the 42nd day of life with 3 mg / kg / day by subcutaneous route of the AMPA receptor antagonist in saline solution and from the 50th day of life with 200 μg / ml riluzole in drinking water until death.
Les résultats obtenus démontrent que la durée de vie est allongée pour les groupes traités par le riluzole seul ou l'antagoniste des récepteurs AMPA seul mais que cette durée est très significativement augmentée de façon inattendue avec l'association riluzole et antagoniste des récepteurs AMPA comparé au riluzole seul et à l'antagoniste des récepteurs AMPA seul.The results obtained demonstrate that the lifespan is longer for the groups treated with riluzole alone or the AMPA receptor antagonist alone, but that this duration is unexpectedly significantly increased with the combination of riluzole and AMPA receptor antagonist compared to riluzole alone and the AMPA receptor antagonist alone.
Lorsque l'antagoniste des récepteurs AMPA est l'acide 9-carboxyméthyl-4,5- dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-phosphonique, les résultats obtenus sont les suivants : When the AMPA receptor antagonist is 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, the results obtained are as follows:
SEM = erreur standard à la moyenneSEM = standard error to the mean
Les composés de l'association peuvent être employés par voie orale, paren- térale, transdermale ou rectale soit simultanément soit séparément soit de manière étalée dans le temps.The compounds of the combination can be used orally, parenterally, transdermally or rectally either simultaneously or separately or spread out over time.
Les associations du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA à l'exception du GYKI52466 et du CNQX sont nouvelles et en tant que telles font partie de l'invention.The combinations of riluzole or one of its pharmaceutically acceptable salts and of one or more AMPA receptor antagonists with the exception of GYKI52466 and CNQX are new and as such form part of the invention.
Les associations préférées sont celles qui contiennent un des antagonistes des récepteurs AMPA précédemment cités, à l'exception du GYKI52466 et du CNQX.The preferred combinations are those which contain one of the AMPA receptor antagonists mentioned above, with the exception of GYKI52466 and CNQX.
La présente invention concerne également les compositions pharmaceutiques comprenant l'association du riluzole et d'un ou plusieurs antagonistes des récepteurs AMPA à l'exception du GYKI52466 et du CNQX, à l'état pur ou sous forme d'une association avec un ou plusieurs diluants et/ou adjuvants compatibles et pharmaceutiquement acceptables et/ou éventuellement en association avec un autre produit pharmaceutiquement compatible et physiologiquement actif.The present invention also relates to pharmaceutical compositions comprising the combination of riluzole and one or more AMPA receptor antagonists with the exception of GYKI52466 and CNQX, in the pure state or in the form of a combination with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants and / or optionally in combination with another pharmaceutically compatible and physiologically active product.
Comme compositions solides pour administration orale, peuvent être utilisés des comprimés, des pilules, des poudres (capsules de gélatine, cachets) ou des granulés. Dans ces compositions, les principes actifs sont mélangés à un ou plusieurs diluants inertes, tels que amidon, cellulose, saccharose, lactose ou silice, sous courant d'argon. Ces compositions peuvent également comprendre des substances autres que les diluants, par exemple un ou plusieurs lubrifiants tels que le stéarate de magnésium ou le talc, un colorant, un enro- bage (dragées) ou un vernis.As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active ingredients are mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.
Comme compositions liquides pour administration orale, on peut utiliser des solutions, des suspensions, des emulsions, des sirops et des élixirs pharmaceutiquement acceptables contenant des diluants inertes tels que l'eau, l'éthanol, le glycérol, les huiles végétales ou l'huile de paraffine. Ces compo- sitions peuvent comprendre des substances autres que les diluants, par exemple des produits mouillants, édulcorants, épaississants, aromatisants ou stabilisants.As liquid compositions for oral administration, there may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin. These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
Les compositions stériles pour administration parentérale, peuvent être de préférence des solutions aqueuses ou non aqueuses, des suspensions ou des emulsions. Comme solvant ou véhicule, on peut employer l'eau, le pro- pylèneglycol, un polyéthylèneglycol, des huiles végétales, en particulier l'huile d'olive, des esters organiques injectables, par exemple l'oléate d'éthyle ou d'autres solvants organiques convenables. Ces compositions peuvent également contenir des adjuvants, en particulier des agents mouillants, isotoni- sants, emulsifiants, dispersants et stabilisants. La stérilisation peut se faire de plusieurs façons, par exemple par filtration aseptisante, en incorporant à la composition des agents stérilisants, par irradiation ou par chauffage. Elles peuvent également être préparées sous forme de compositions solides sté- riles qui peuvent être dissoutes au moment de l'emploi dans de l'eau stérile ou tout autre milieu stérile injectable.The sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or the like, can be used. suitable organic solvents. These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions. riles which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
Les compositions pour administration rectale sont les suppositoires ou les capsules rectales qui contiennent, outre le produit actif, des excipients tels que le beurre de cacao, des glycérides semisynthétiques ou des polyéthy- lèneglycols.The compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
La présente invention concerne également la méthode de prévention et/ou de traitement des patients atteints de sclérose latérale amyotrophique qui consiste à administrer au patient une association du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA soit simultanément soit séparément soit de manière étalée dans le temps.The present invention also relates to the method of prevention and / or treatment of patients suffering from amyotrophic lateral sclerosis which consists in administering to the patient a combination of riluzole or one of its pharmaceutically acceptable salts and of one or more antagonists of AMPA receptors, either simultaneously either separately or spread out over time.
Les doses dépendent de l'effet recherché, de la durée du traitement et de la voie d'administration utilisée; elles sont généralement de 10 à 400 mg par jour par voie orale pour un adulte avec des doses unitaires allant de 10 à 200 mg de riluzole et de 5 à 100 mg par jour par voie sous-cutanée ou trans- dermale pour un adulte avec des doses unitaires de 1 à 50 mg de l'antagoniste des récepteurs AMPA.The doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally from 10 to 400 mg per day orally for an adult with unit doses ranging from 10 to 200 mg of riluzole and from 5 to 100 mg per day by subcutaneous or transdermal route for an adult with unit doses of 1 to 50 mg of the AMPA receptor antagonist.
D'une façon générale, le médecin déterminera la posologie appropriée en fonction de l'âge, du poids et de tous les autres facteurs propres au sujet à traiter. In general, the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.

Claims

REVENDICATIONS
1 - Utilisation d'une association de riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA pour la préparation d'un médicament utile pour la prévention et/ou le traitement de la sclérose latérale amyotrophique.1 - Use of a combination of riluzole or one of its pharmaceutically acceptable salts and of one or more antagonists of AMPA receptors for the preparation of a medicament useful for the prevention and / or the treatment of amyotrophic lateral sclerosis.
2 - Utilisation selon la revendication 1 pour la préparation d'un médicament comprenant 10 à 400 parties en poids de riluzole pour 5 à 100 parties en poids de l'antagoniste des récepteurs AMPA.2 - Use according to claim 1 for the preparation of a medicament comprising 10 to 400 parts by weight of riluzole per 5 to 100 parts by weight of the AMPA receptor antagonist.
3 - Utilisation selon l'une des revendications 1 ou 2 pour la préparation d'un médicament pour une utilisation simultanée, séparée ou étalée dans le temps.3 - Use according to one of claims 1 or 2 for the preparation of a medicament for simultaneous use, separate or spread over time.
4 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one de formule :4 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is chosen from 5H, 10H-imidazo [1, 2-a] indeno [1, 2 derivatives -e] pyrazine-4-one of formula:
dans laquellein which
- R représente un radical N-alk, C(R4)R5, CH-Rg ou C=R7,- R represents an N-alk, C (R4) R5, CH-Rg or C = R7 radical,
- R-| et R2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux alkyle, alcoxy, amino, -N=CH-N(alk)alk', nitro, cyano, phényle, imidazolyle, SO3H, hydroxy, polyfluoroalcoxy, carboxy, alcoxycarbonyle, -NH-CO-NR-i 1 R-| 2, -N(alk)-CO-NRι 1 R-| 2, -N(alk-Ar)-CO-NR-| -|Ri2, -NH-CS-NRι ιR12, -N(alk)-CS-NRι -|R-|2, -NH-CO-R-i 1 , -NH-CS-R24, -NH-C(=NR 7)-NR-| 0R-| 2, -N(alk)-C(=NR27)-NR-|QR-|2, -CO-NR-|0R-|2, -NH-SO2-NR10R12,- R- | and R2, which may be identical or different, represent hydrogen or halogen atoms or alkyl, alkoxy, amino, -N = CH-N (alk) alk ', nitro, cyano, phenyl, imidazolyl, SO3H, hydroxy, polyfluoroalkoxy, carboxy, alkoxycarbonyl, -NH-CO-NR-i 1 R- | 2, -N (alk) -CO-NRι 1 R- | 2, -N (alk-Ar) -CO-NR- | - | Ri2, -NH-CS-NRι ιR 12 , -N (alk) -CS-NRι - | R- | 2 , -NH-CO-Ri 1, -NH-CS-R24, -NH-C (= NR 7) -NR- | 0 R- | 2 , -N (alk) -C (= NR 2 7) -NR- | QR- | 2, -CO-NR- | 0 R- | 2, -NH-SO2-NR10R12,
-N(alk)-SO2-NR10R-|2I -NH-SO2-CF3, -NH-S02-alk, -NR10R13, -S(0)m-alk-Ar, -SO2-NR10R-12, 2-oxo-1-imidazolidinyle dont la position -3 est éventuellement substituée par un radical alkyle ou 2-0x0-1 -perhydropyrimidinyle dont la position -3 est éventuellement substi- tuée par un radical alkyle,-N (alk) -SO 2 -NR 10 R- | 2 I -NH-SO2-CF3, -NH-S0 2 -alk, -NR10R13, -S (0) m -alk-Ar, -SO2-NR10R- 12, 2-oxo-1-imidazolidinyl whose position -3 is optionally substituted by an alkyl radical or 2-0x0-1 -perhydropyrimidinyl whose position -3 is optionally substituted by an alkyl radical,
- R3 représente un atome d'hydrogène ou un radical carboxy, alcoxycarbonyle ou carboxamido,- R3 represents a hydrogen atom or a carboxy, alkoxycarbonyl or carboxamido radical,
- R4 représente un radical alkyle, -alk-Het ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choi- sis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COOR-|Q,- R4 represents an alkyl, -alk-Het or phenylalkyl radical, the phenyl nucleus of which is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano radicals, - alk-NH2, -COOR-I Q and -alk-COOR- | Q,
- R5 représente un radical alkyle (1-11C en chaîne droite ou ramifiée), -alk-Het, -NR8Rg, -NH-CHO, -NH-COOR17, -NH-SO2R24. -COOR10, -alk-COOR-jQ, -alk-CONR-ioR-is, -alk-NR-|QR-|8, -alk-OH, -alk-CN, phénylal- kyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-JO et -alk-COOR-iQ, -NH-CO-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COORio, -NH-CO-Het, -NH-CO-alk-Het, -NH-CO-alk-COOR10, -NH-CO-alk-NR-|θR-|8, -NH-CO-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-IQ et -alk-COOR-| Q, pyrrol-1-yle éventuellement substitué par un radical -COOR-| Q, -NH-CO-NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-| Q et -alk-COOR-|Q, -NH-CO-NH-Het, -NH-CO-NH-alk-Het, -NH-CO-NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COORIQ et -alk-COORiQ, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH-alk ou -NH-CO-NH2,- R5 represents an alkyl radical (1-11C in a straight or branched chain), -alk-Het, -NR 8 Rg, -NH-CHO, -NH-COOR17, -NH-SO2R24. -COOR 10 , -alk-COOR-jQ, -alk-CONR-ioR-is, -alk-NR- | QR- | 8, -alk-OH, -alk-CN, phenylalkyl, the phenyl ring of which is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-JO and -alk-COOR-iQ, -NH-CO- radicals Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q and -alk-COORio radicals, - NH-CO-Het, -NH-CO-alk-Het, -NH-CO-alk-COOR 10 , -NH-CO-alk-NR- | θR- | 8, -NH-CO-alk-Ar of which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-IQ and -alk-COOR- radicals | Q, pyrrol-1-yl optionally substituted with a radical -COOR- | Q, -NH-CO-NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, - COOR- | Q and -alk-COOR- | Q, -NH-CO-NH-Het, -NH-CO-NH-alk-Het, -NH-CO-NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COORIQ and -alk-COORiQ, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH- radicals alk or -NH-CO-NH2,
ou bien R4 et R5 forment ensemble avec l'atome de carbone auquel ils sont rattachés (a) un cycle 2- ou 3-pyrrolidine, un cycle 2- ou 4-pipéridine ou un cycle 2-azacycloheptane, ces cycles étant éventuellement substitués sur l'azote par un radical alkyle, -CHO, -COOR11 , -CO-alk-COORg, -CO-alk-NRgR-12, -CO-alk-CONRgR8, -CO-COORg, -CO-CH2-0-CH2-COORg, -CO-CH2-S-CH2-COORg, -CO-CH=CH-COORg, -CO-alk, -CO-Ar", -CO-alk-Ar", -CO-NH-Ar", -CO-NH-alk-Ar", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH , -CO-NH-alk, -CO-N(alk)alk', -CS-NH2, -CS-NH-alk, -CS-NH-Ar", -CS-NH-Het, -alk-Het, -alk-NRgRg, -alk-COORg, -alk-CO-NRgRg, -alk-Ar", -Sθ2-alk, -Sθ2-Ar ou -CO-cycloalkyle dont le cycloalkyle est éventuellement substitué en -2 par un radical carboxy, (b) un cycle 2-pyrrolidine-5-one ou (c) un cycloalkyle,or else R4 and R5 form together with the carbon atom to which they are attached (a) a 2- or 3-pyrrolidine ring, a 2- or 4-piperidine ring or a 2-azacycloheptane ring, these rings being optionally substituted on nitrogen via an alkyl radical, -CHO, -COOR11, -CO-alk-COORg, -CO-alk-NRgR-12, -CO-alk-CONRgR 8 , -CO-COORg, -CO-CH2-0- CH 2 -COORg, -CO-CH2-S-CH 2 -COORg, -CO-CH = CH-COORg, -CO-alk, -CO-Ar ", -CO-alk-Ar", -CO-NH- Ar ", -CO-NH-alk-Ar", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH, -CO-NH -alk, -CO-N (alk) alk ', -CS-NH 2 , -CS-NH-alk, -CS-NH-Ar ", -CS-NH-Het, -alk-Het, -alk-NRgRg , -alk-COORg, -alk-CO-NRgRg, -alk-Ar ", -Sθ2-alk, -Sθ2-Ar or -CO-cycloalkyle the cycloalkyl of which is optionally substituted at -2 by a carboxy radical, (b) a 2-pyrrolidine-5-one ring or (c) a cycloalkyl,
- Rg représente un atome d'hydrogène ou un radical hydroxy, alkyle (1-11C en chaîne droite ou ramifiée), -alk-OH, -NR-14R15, -alk-NR-|4R-|5, -alk-Het, -NH-CHO, -COOalk, -alk-COOR-|Q, -alk-CO-NR-|oR2i , phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COOR-io, -R-lg-COOR-iQ, -CO-COOR-I Q, pyrrol-1-yle éventuellement substitué par un radical -COOR-I Q ou 2-oxo-2,5-dihydropyrrol-1-yle, - R7 représente un atome d'oxygène ou un radical NOH, NO-alk-COOR-iQ, NO-alk, CHR-jg, NR10, C(COORI Q)R20 OU C(CONR-| QR2I )R20.- Rg represents a hydrogen atom or a hydroxy radical, alkyl (1-11C in straight or branched chain), -alk-OH, -NR-14R15, -alk-NR- | 4R- | 5, -alk-Het , -NH-CHO, -COOalk, -alk-COOR- | Q, -alk-CO-NR- | oR2i, phenylalkyl in which the phenyl ring is optionally substituted by one or more substituents chosen from halogen atoms and radicals alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q and -alk-COOR-io, -R-lg-COOR-i Q , -CO-COOR-I Q, pyrrol- 1-yl optionally substituted by a radical -COOR-I Q or 2-oxo-2,5-dihydropyrrol-1-yl, - R7 represents an oxygen atom or a radical NOH, NO-alk-COOR-iQ, NO-alk, CHR-jg, NR 10 , C (COORI Q) R20 OR C (CONR- | QR2I) R20.
- R8 représente un atome d'hydrogène ou un radical alkyle, -alk-COOR-jQ, -alk-NRiQR2i , -alk-Het ou phénylalkyle dont le noyau phényle est éventuel- lement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COOR-jQ,- R8 represents a hydrogen atom or an alkyl, -alk-COOR-jQ, -alk-NRiQR2i, -alk-Het or phenylalkyl radical, the phenyl nucleus of which is optionally substituted by one or more substituents chosen from atoms halogen and the alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q and -alk-COOR-jQ radicals,
- Rg représente un atome d'hydrogène ou un radical alkyle,- Rg represents a hydrogen atom or an alkyl radical,
- R-| Q représente un atome d'hydrogène ou un radical alkyle,- R- | Q represents a hydrogen atom or an alkyl radical,
- R-| 1 représente un atome d'hydrogène ou un radical alkyle (1-9C en chaîne droite ou ramifiée), -alk-COOR-jQ, -alk-Het, -alk-NR-|2Rιo, phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-i Q, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-iQ Ou -Het,- R- | 1 represents a hydrogen atom or an alkyl radical (1-9C in a straight or branched chain), -alk-COOR-jQ, -alk-Het, -alk-NR- | 2Rιo, phenylalkyl in which the phenyl nucleus is optionally substituted with one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR-i Q radicals, phenyl optionally substituted by one or several substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR-iQ Ou -Het radicals,
- R-12 représente un atome d'hydrogène ou un radical alkyle,- R-12 represents a hydrogen atom or an alkyl radical,
- R13 représente un radical alkyle, Het ou alcoxycarbonyle,- R13 represents an alkyl, Het or alkoxycarbonyl radical,
- R-I4 et R15, identiques ou différents représentent chacun un radical alkyle ou bien R14 représente un atome d'hydrogène et R15 représente un atome d'hydrogène ou un radical alkyle, -COR22> -CSR23 ou -SO2R24.- R-I4 and R15, identical or different, each represent an alkyl radical or else R14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl radical, -COR22 > -CSR23 or -SO2R24.
- R-| g représente une chaîne -CHOH- ou -CH(OH)-alk(1-5C)-,- R- | g represents a chain -CHOH- or -CH (OH) -alk (1-5C) -,
- R17 représente un radical alkyle ou phénylalkyle, - R-|8 représente un atome d'hydrogène ou un radical alkyle,- R17 represents an alkyl or phenylalkyl radical, - R- | 8 represents a hydrogen atom or an alkyl radical,
- R-|g représente un radical hydroxy, alkyle, -alk-Het, -NR2δR26> -alk-COOR-|Q, -Het, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, al- coxy, nitro, amino, hydroxy, -alk-NH2, -COOR-io, cyano et -alk-COOR-|Q ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano et -alk-COOR-iQ,- R- | g represents a hydroxy, alkyl, -alk-Het, -NR2δR26 > -alk-COOR- | Q, -Het, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl radicals , alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-io, cyano and -alk-COOR- | Q or phenylalkyl, the phenyl ring of which is optionally substituted by one or more substituents chosen from atoms of halogen and the alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano and -alk-COOR-iQ radicals,
- R20 représente un atome d'hydrogène ou un radical alkyle,- R20 represents a hydrogen atom or an alkyl radical,
- R21 représente un atome d'hydrogène ou un radical alkyle,- R21 represents a hydrogen atom or an alkyl radical,
- R22 représente un radical alkyle, cycloalkyle, -COOalk, -alk-COOR-jo, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hy- droxy, -alk-NH2, -COOR-IQ, cyano et -alk-COOR-jo, phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano et -alk-COOR-|o, -alk-NR-|QR-|2, -NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-| Q, cyano et -alk-COOR-io, -Het, -alk-Het, -OR17, -NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano et -alk-COOR-jo, -NH-alk-Het, -NH-alk, -NH2 ou -NH-Het,- R22 represents an alkyl, cycloalkyl, -COOalk, -alk-COOR-jo, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy radicals, - alk-NH2, -COOR-IQ, cyano and -alk-COOR-jo, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy radicals , -alk-NH2, -COOR-I Q, cyano and -alk-COOR- | o, -alk-NR- | QR- | 2, -NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR- radicals | Q, cyano and -alk-COOR-io, -Het, -alk-Het, -OR17, -NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl radicals, alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano and -alk-COOR-jo, -NH-alk-Het, -NH-alk, -NH2 or -NH-Het,
- R23 représente un radical -NH-alk, -NH-Ar, -NH-Het ou -NH2,- R23 represents a radical -NH-alk, -NH-Ar, -NH-Het or -NH2,
- R24 représente un radical alkyle ou phényle, - R25 et R2g, identiques ou différents, représentent chacun un radical alkyle ou cycloalkyle,- R24 represents an alkyl or phenyl radical, - R25 and R2g, identical or different, each represent an alkyl or cycloalkyl radical,
- R27 représente un atome d'hydrogène ou un radical alkyle,- R27 represents a hydrogen atom or an alkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
- alk' représente un radical alkyle,- alk 'represents an alkyl radical,
- m est égal à 0, 1 ou 2,- m is equal to 0, 1 or 2,
- Ar représente un radical phényle,- Ar represents a phenyl radical,
- Het représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes (O, S, N) éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle,Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms (O, S, N) optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
les radicaux et portions alkyle, alkylène et alcoxy contiennent 1 à 6 atomes de carbone et sont en chaîne droite ou ramifiée, les radicaux et portions acyle contiennent 2 à 4 atomes de carbone, les radicaux cycloalkyle contiennent 3 à 6 atomes de carbone et les atomes d'halogène sont choisis parmi le fluor, le chlore, le brome et l'iode,alkyl, alkylene and alkoxy radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain, acyl radicals and portions contain 2 to 4 carbon atoms, cycloalkyl radicals contain 3 to 6 carbon atoms and the atoms of halogen are chosen from fluorine, chlorine, bromine and iodine,
les isomères (E et Z) et leurs mélanges des composés pour lesquels R7 représente un radical NO-alk, C(COOR-|o)R2θ, C(CONR-| QR2I )R20 OU CHR-|g, les formes tautomères (E et Z) des composés pour lesquels R re- présente un radical CH-Rg et Rg représente un radical -CO-COOR-I Q, les énantiomères et diastéréoisomères des composés pour lesquels R représente un radical C(R4)R5 ou CH-Rgthe isomers (E and Z) and their mixtures of the compounds for which R7 represents a radical NO-alk, C (COOR- | o) R2θ, C (CONR- | QR2I) R20 OR CHR- | g, the tautomeric forms (E and Z) of the compounds for which R represents a radical CH-Rg and Rg represents a radical -CO-COOR-I Q, the enantiomers and diastereoisomers of the compounds for which R represents a radical C (R4) R5 or CH-Rg
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
5 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one de formule :5 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is chosen from 5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one derivatives of formula:
-R'-R '
dans laquelle,in which,
- R' représente un atome d'hydrogène ou un radical carboxy, alcoxycarbonyle, -CO-NR'4R'5, -P03H2 ou -CH2OH,- R 'represents a hydrogen atom or a carboxy, alkoxycarbonyl, -CO-NR'4R' 5 , -P0 3 H 2 or -CH 2 OH radical,
- R'-| représente un radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR'5R'g ou -CO-NH-R'7,- R'- | represents a radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR ' 5 R'g or -CO-NH-R'7,
- R'3 représente un radical alkyle, phényle, phénylalkyle, cycloalkyle ou -NR'gR's,- R'3 represents an alkyl, phenyl, phenylalkyl, cycloalkyl or -NR'gR's radical,
- R'4 représente un atome d'hydrogène ou un radical alkyle,- R'4 represents a hydrogen atom or an alkyl radical,
- R 5 représente un atome d'hydrogène ou un radical alkyle, phényle, cycloalkyle ou phénylalkyle,R 5 represents a hydrogen atom or an alkyl, phenyl, cycloalkyl or phenylalkyl radical,
- R'g représente un atome d'hydrogène ou un radical alkyle,- R'g represents a hydrogen atom or an alkyl radical,
ou bien R'5 et R'g forment avec l'atome d'azote auquel ils sont rattachés un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 6 atomes de carbone et éventuellement un ou plusieurs autres hétéroatomes choisis parmi O, S, N, - R'7 représente un radical phényle, phénylalkyle ou -alk-COOR'4,or else R'5 and R'g form, with the nitrogen atom to which they are attached, a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 6 carbon atoms and optionally one or more other heteroatoms chosen from O, S, N , - R'7 represents a phenyl, phenylalkyl or -alk-COOR'4 radical,
- R'8 représente un atome d'hydrogène ou un radical alkyle, cycloalkyle ou phénylalkyle,R'8 represents a hydrogen atom or an alkyl, cycloalkyl or phenylalkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
les radicaux et portions alcoxy, alkyle et alkylène contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée et les radicaux cycloalkyle contiennant 3 à 6 atomes de carbonealkoxy, alkyl and alkylene radicals and portions containing 1 to 6 carbon atoms in a straight or branched chain and cycloalkyl radicals containing 3 to 6 carbon atoms
leurs énantiomères et stéréoisomères et leurs sels pharmaceutiquement acceptables.their enantiomers and stereoisomers and their pharmaceutically acceptable salts.
6 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one de formule :6 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is chosen from 5H, 10H-imidazo derivatives [1, 2-a] indeno [1, 2 -e] pyrazine-4-one of formula:
dans laquellein which
R" représente un atome d'hydrogène ou un radical -COOH, -alk-COOH, -PO3H2, -CH2-P03H2, -CH=CH-COOH ou phényle substitué par un radical carboxy, R"1 représente un radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H ou -alk-C0-NH-S02R"2,R "represents a hydrogen atom or a radical -COOH, -alk-COOH, -PO3H2, -CH2-P03H2, -CH = CH-COOH or phenyl substituted by a carboxy radical, R "1 represents a radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H or -alk-C0-NH-S02R" 2,
R"2 représente un radical alkyle ou phényle,R "2 represents an alkyl or phenyl radical,
alk représente un radical alkyle,alk represents an alkyl radical,
Het représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes choisis parmi O, S, N, Phétérocycle étant éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle,Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms chosen from O, S, N, the heterocycle being optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
les radicaux alkyle et alcoxy contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée,alkyl and alkoxy radicals containing 1 to 6 carbon atoms in a straight or branched chain,
les isomères (E et Z) des composés pour lesquels R représente un radical -CH=CH-COOH, les racémiques, énantiomères et diastéréoisomères des composés pour lesquels R représente un radical -alk-COOH et/ou R, représente un radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H2 ou -alk-C0-NH-S02R2the isomers (E and Z) of the compounds for which R represents a radical -CH = CH-COOH, the racemates, enantiomers and diastereoisomers of the compounds for which R represents a radical -alk-COOH and / or R represents a radical -alk -CN, -alk-COOH, -alk-Het, -alk-P03H2 or -alk-C0-NH-S02R2
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
7 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de pyrazine-2,3-dione de formule :7 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is chosen from pyrazine-2,3-dione derivatives of formula:
dans laquelle - R'" représente un radical C(R"'4)R'"5, CH-R"'g ou C=R'"7,in which - R '"represents a radical C (R"' 4) R '" 5 , CH-R"' g or C = R '" 7 ,
- R"'-| et R'"2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux amino, nitro ou -NH-CO-NR"'-| -| R"'i2,- R "'- | and R'" 2, identical or different, represent hydrogen or halogen atoms or amino, nitro or -NH-CO-NR "" - | - | R "'i2,
- R'"3 représente un atome d'oxygène,- R '"3 represents an oxygen atom,
- R'"4 représente un radical alkyle,- R '"4 represents an alkyl radical,
- R"'5 représente un radical -alk-COOR'"iQ,- R "'5 represents a radical -alk-COOR'" iQ,
- R"'g représente un atome d'hydrogène ou un radical -NR"'-|4R'"i5,- R "'g represents a hydrogen atom or a radical -NR"' - | 4R '"i5,
- R'"7 représente un radical NOH ou C(COOR"'I Q)R"'2O,- R '"7 represents a NOH or C (COOR"' I Q) R "'2O radical,
- R'"ιo représente un atome d'hydrogène ou un radical alkyle,- R '"ιo represents a hydrogen atom or an alkyl radical,
- R"'-| -| représente phényle,- R "'- | - | represents phenyl,
- R"'-|2 représente un atome d'hydrogène,- R "'- | 2 represents a hydrogen atom,
- R"'-|4 représente un atome d'hydrogène,- R "'- | 4 represents a hydrogen atom,
- R"'-|5 représente un atome d'hydrogène ou un radical -COR'"22.- R "'- | 5 represents a hydrogen atom or a radical -COR'" 22.
- R"'20 représente un atome d'hydrogène,- R "'20 represents a hydrogen atom,
- R'"22 représente un radical alkyle,- R '"22 represents an alkyl radical,
- alk représente un radical alkyle,- alk represents an alkyl radical,
les radicaux et portions alkyle contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée et les atomes d'halogène étant choisis parmi le fluor, le chlore, le brome et l'iode,the radicals and alkyl portions containing 1 to 6 carbon atoms in a straight or branched chain and the halogen atoms being chosen from fluorine, chlorine, bromine and iodine,
les isomères (E et Z) des composés pour lesquels R"' représente un radical C=R'"7 et R'"7 représente un radical C(COOR'"ιo)R"'2o, les énantiomères et diastéreoisomeres des composés de formule (I) pour lesquels R représente un radical C(R4)R5 ou CH-Rg,the isomers (E and Z) of the compounds for which R "'represents a radical C = R'" 7 and R '"7 represents a radical C (COOR'" ιo) R "'2o, the enantiomers and diastereoisomers of the compounds of formula (I) for which R represents a radical C (R4) R5 or CH-Rg,
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
8 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est choisi parmi les composés suivants :8 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is chosen from the following compounds:
8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 8-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-phényl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(1 -imidazolyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 4-oxo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-sulfonique, 7-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-bromo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 6,7-dichloro-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,8-dichloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8,9-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,9-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro 9-bromo-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-méthoxy-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 5H,10H-8-amino-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-(3-phényluréido)-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-acétamido-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-diméthylaminométhylèneamino-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 7-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxy-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-acétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(E-diméthylaminométhylène)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine -4-one, 10-hydroxyméthylène-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-è]pyrazine-4-one, 10, 10-diméthyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10:1'-cyclopropane]-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10: 1 '-cyclopentane]-4-one, 10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxyméthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-furylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-pyridylméthylène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(phénylpropyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-pyridylméthylène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-imidazolylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide (4-oxo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)amino- oxyacétique,8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-phenyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (1 -imidazolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 4-oxo-5H acid, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -8-sulfonic, 7-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-bromo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-fluoro-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 6,7-dichloro-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one , 7,8-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8,9-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7,9-dichloro-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro 9-bromo-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5H, 10H-8-methoxy-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 5H, 10H-8-amino-imidazo [1,2-a] indeno [ 1, 2-e] pyrazine-4-one, 5H, 10H-8- (3-phenylureido) -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-acetamido-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-dimethylaminomethyleneamino-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxy-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (E-dimethylaminomethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -4-one, 10-hydroxymethylene-5HJ0H-imidazo [1, 2-a] indeno [1, 2-è] pyrazine-4-one, 10, 10-dimethyl-5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10: 1 '-cyclopropane] -4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10: 1' -cyclopentane] -4-one, 10-methyl-5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxymethyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine -4-one, 10- (2-furylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazin e-4-one, 10- (4-pyridylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (phenylpropyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-pyridylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 10- (2-imidazolylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-isobutyl-5H, 10H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid (4-oxo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 10-ylidene) amino-oxyacetic,
10-propionamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyramido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-7-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzènesulfonylamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyrazinylméthylène)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,10-propionamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- isobutyramido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-7-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-benzenesulfonylamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-pyrazinylmethylene ) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one,
10-(2-pyrazinylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 10-méthyl-10-(4-pyridylméthyl)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine- 4-one,10- (2-pyrazinylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one, 10-methyl-10- (4-pyridylmethyl) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine- 4-one,
10-(4-pipéridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzyl-7-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione, 10-(3-phényluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-(3-phényluréido)-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4- one,10- (4-piperidylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-benzyl-7-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4,10-dione, 10- (3 -phenylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-10- (3-phenylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one,
10-méthyl-10-[2-(pyridine-4-yl)éthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] py- razine-4-one, 9-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-éthoxycarbonylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-cyanophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(3-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,10-methyl-10- [2- (pyridine-4-yl) ethyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-phenylacetamido -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e ] pyrazine-4-one, 8- [3- (3-cyanophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3 - (3-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one,
8-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-tert-butyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-benzylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-tert-butylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-benzamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(4-phénylbutyrylamino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(5-phénylvalérylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (4-phenylbutyrylamino-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 8- (5-phenylvalerylamino-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one,
8-(3-éthoxycarbonylméthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,8- (3-ethoxycarbonylmethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-carboxyméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(3,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-è]pyrazine-4-one,8- (3-carboxymethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (3,3-dimethylureido) -5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-è] pyrazine-4-one,
8-hydroxy-5HJ0H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,8-hydroxy-5HJ0H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one,
8-(3-aminopropionamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-aminopropionamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-aminoacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-aminoacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-nitrophényl)uréido]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-nitrophenyl) ureido] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- [3- (2-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
8-[3-(2-nitrophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-aminophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-nitrophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-aminophenyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- [3- (4-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
8-(4-méthylpentanoyl)amino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4 one,
N,N-diméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- sulfonamide,N, N-dimethyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-sulfonamide,
8-(3-phénylthiouréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-phenylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-méthylthiouréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(2-oxo-1-imidazolinyl)-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-formamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (2-oxo-1-imidazolinyl) -5HJ0H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-éthoxycarbonylpropionylamino)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- (3-ethoxycarbonylpropionylamino) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-éthoxycarbonyléthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- [3- (2-ethoxycarbonylethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-carboxyéthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- [3- (2-carboxyethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one,
8-[3-(4-fluorophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(3-fluorophényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (3-fluorophenyl) ureido ] -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one,
8-[3-(2-fluorophényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-fluorophenyl) ureido] -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4- one,
8-(3-éthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one, 8-[3-morpholino-uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-ethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3-morpholino-ureido] -5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10-amino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-hydroxyimino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione,10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4,10-dione,
8-[3-(3-aminophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one-8-carboxylique,8- [3- (3-aminophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5H acid, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one-8-carboxylic,
8-uréido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(2-aminoéthyl)thiouréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8-ureido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (2-aminoethyl) thiouréido] -5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4- one,
8-thiouréido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-thiouréido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-imidazoline-2-yl)amino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[(1 -pyrrolidinyl)carbonylamino]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazi- ne-4-one,8 - [(2-imidazoline-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8 - [(1 -pyrrolidinyl) carbonylamino] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(1 -azétidinyl)carbonylamino]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazi-ne-8 - [(1 -azetidinyl) carbonylamino] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazi-ne-
4-one, 8-(3-propyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,4-one, 8- (3-propyluréido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-isopropyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one,8- (3-isopropylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-(3-butyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-butylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-thiazolin-2-yl)amino]-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(1 ,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8 - [(2-thiazolin-2-yl) amino] -5HJOH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (1, 3-dimethylureido) -5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-carbométhoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- [3- (3-carbomethoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-carboxyphenyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carbométhoxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- [3- (4-carbomethoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(4-carboxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carboxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorobenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-fluorobenzyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
9-carboxy-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one,9-carboxy-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one,
9-carboxamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9-carboxamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-diéthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-(N-éthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 8-[3-(4-méthoxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 8-méthylsulfonamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one-10-carboxylate d'éthyle, 10-imino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-carboxybenzyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-carboxybenzylidène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,9- (N-diethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 8- [3- (4-methoxybenzyl) ureido] -5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one, 8-methylsulfonamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4 -one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-4-one-10-carboxylate, 10-imino-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 10- (2-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-carboxybenzylidene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-(3-carboxybenzyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-[(1-méthylimidazol-2-yl)méthylène]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 10-(carboxyméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(carboxyméthylène)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 5-(4-hydroxy-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)penta- noïque, 10-(1-carboxy-1-hydroxyméthyl)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,10- (3-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-aminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10 - [(1-methylimidazol-2-yl) methylene] -5H, 10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-4-one, 10- (carboxymethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (carboxymethylene) -5HJ 0H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5- (4-hydroxy-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10- ylidene) pentanoic, 10- (1-carboxy-1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-nicotinoylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 3-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)amino- carbonyljpropionate de méthyle, 10-(3-diéthylaminopropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,10-nicotinoylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 3- [10- (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazinyl) methyl amino-carbonylpropionate, 10- (3-diethylaminopropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-formamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, (10R)-10[(R)-α-méthoxy-α-trifluorométhylphénylacétamido]-5H,10H-imida- zo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, (10S)-10[(R)-α-méthoxy-α-trifluorométhylphénylacétamido]-5H,10H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (10R) -10 [(R) -α-methoxy-α-trifluoromethylphenylacetamido] -5H , 10H-imida- zo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (10S) -10 [(R) -α-methoxy-α-trifluoromethylphenylacetamido] -5H, 10H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
N-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]carba- mate de tert-butyle,N- [10- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] tert-butyl carbamate,
10-(1-pyrrolyl)-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 1 -[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]pyrrole-2- carboxylate de méthyle,10- (1-pyrrolyl) -5HJ0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 1 - [10- (4,5-dihydro-4-oxo-10H- imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] methyl pyrrole-2-carboxylate,
10-méthoxyimino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-methoxyimino-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-acétamido-10-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-acetamido-10-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 10-(4-imidazolylméthyl)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-methyl-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 10- (4-imidazolylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(carboxyméthylène)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one, 10-amino-10-méthyl-8-(3-n-propyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one,10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-4-one, 10-amino-10-methyl-8- (3-n-propyluréido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-(3-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (3-aminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-aminobenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (3-aminobenzylidene) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-acétylaminobenzyl)-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 10-(3-méthoxycarbonylbenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- (3-acetylaminobenzyl) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 10- (3-methoxycarbonylbenzylidene) -5H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-
4-one,4-one,
10-amino-10-(3-phénylpropyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 5-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-10-yl)valérique,10-amino-10- (3-phenylpropyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5- (10-methyl-4,5- dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl) valeric,
4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyrazine-10- yl)butyronitrile, acide 4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)butyrique, 10-hydroxyméthyl-10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one, acide (10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)acétique, 3-( 10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- yl)propionitrile, acide 3-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)propionique,4- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyronitrile, acid 4- (10- methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyric, 10-hydroxymethyl-10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one, acid (10-methyl-4,5-dihydro-4-oxo- 10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) acetic, 3- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-10-yl) propionitrile, 3- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo acid [1, 2, -a ] indeno [1, 2-e] pyrazine-10-yl) propionic,
10-méthyl-10-[(1-méthylimidazol-2-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno [1 ,2-e]pyrazine-4-one,10-methyl-10 - [(1-methylimidazol-2-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-[(1-méthylimidazol-5-yl)méthylène]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10 - [(1-methylimidazol-5-yl) methylene] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-[(1-méthylimidazol-5-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one, 8-[3-(3-fluorophényl)uréido]-10-(carboxyméthyl)-5H,10H-imidazo[1,2-a]indé- no[1 ,2-e]pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno [1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno10 - [(1-methylimidazol-5-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3 -fluorophenyl) ureido] -10- (carboxymethyl) -5H, 10H-imidazo [1,2-a] indeno-no [1,2-e] pyrazine-4-one, acid [8- (3-methylureido) - 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (+) [8- (3-methyluréido) -4 , 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3-methyluréido) -4, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-10-yl]acétique, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-yl) gly- colique, 10-méthyl-10-(1-pyrrolyl)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, acide 1 -[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)] pyrrole-2-carboxylique, acide 3-[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyljpropionique, 10-amino-10-éthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-10-benzyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,[1, 2-e] pyrazine-10-yl] acetic, acid (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl ) glycolic, 10-methyl-10- (1-pyrrolyl) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, acid 1 - [10- ( 4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] pyrrole-2-carboxylic acid 3- [10- (4-oxo-4, 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyljpropionic, 10-amino-10-ethyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-10-benzyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-propyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]propionique, N-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zinyl)]carbamate de tert-butyle, acide 4-[10-(10-méthyl-4-oxo-4,5-dihydro-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]butyrique,10-amino-10-propyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid 3- [10- (10-methyl-4-oxo-4 , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic, N- [10- (10-methyl-4-oxo-4,5-dihydro-10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] tert-butyl carbamate, 4- [10- (10-methyl-4-oxo-4,5-dihydro-1 acid) OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] butyric,
10-amino-10-isopropyl-5H,1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-10-butyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-isopropyl-5H, 1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-10-butyl-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one,
10-méthyl-10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10-methyl-10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one et ses énantiomères, 10-(1 ,3-diméthyl-1 H-pyrazole-4-méthylène)-5H,10H-imidazo[1 ,2-a]indéno10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-4-one and its enantiomers, 10- (1, 3-dimethyl-1 H-pyrazole-4-methylene) -5H, 10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-4-one, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imidazo[1, 2-e] pyrazine-4-one, 3- {10- [10-methyl-8- (3-methylureido) -4-oxo-4,5-dihydro-1 OH-imidazo acid
[1 ,2-a]indéno[1 ,2-e]ρyrazinyl]aminocarbonyl}propionique,[1, 2-a] indeno [1, 2-e] ρyrazinyl] aminocarbonyl} propionic,
(10'RS)-spiro[pyrrolidine-3,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,(10'RS) -spiro [pyrrolidine-3,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one,
(lO'RSJ-spirotpipéridine^.lO'-δΗ.IO'H-imidazofl^-aJindénotl ^-ejpyrazine]-(lO'RSJ-spirotpiperidine ^ .lO'-δΗ.IO'H-imidazofl ^ -aJindénotl ^ -ejpyrazine] -
4'-one,4'-one,
(10'RS)-spiro[pyrrolidine-2,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one, (10'RS)-1 -méthyl-spiro[pyrrolidine-2,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -spiro [pyrrolidine-2,10'-5'H, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one, (10 ' RS) -1-methyl-spiro [pyrrolidine-2,10'-5'H, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one,
(+)-1-méthyl-spiro[pyrrolidine-2,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine]-4'-one,(+) - 1-methyl-spiro [pyrrolidine-2,10'-5'H, 10Η-imidazo [1, 2-a] indéno [1, 2-e] py- razine] -4'-one,
(-)-1-méthyl-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1,2-e]py- razine]-4'-one, acide (lO'RSJ^-oxo^^'-oxo^'.δ'-dihydro-spirotpyrrolidine^.lO'-IO'H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique, spiro[pipéridine-4, 10'-5'H, 10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one, acide 4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pipéridine-4, 10'-10'H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-1 -yl]}butyrique, l-phénylacétyl-spirofpipéridine^lO'-δ'H.IO'H-imidazofl ^-ajindénofl ^-e] yrazine]-4'-one,(-) - 1-methyl-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1,2-e] py- razine] -4'-one, acid (lO'RSJ ^ -oxo ^^ '- oxo ^'. δ'-dihydro-spirotpyrrolidine ^ .lO'-IO'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -1 -yl]} - butyric, spiro [piperidine-4, 10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, 4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [piperidine-4, 10'-10'H-imidazo [1, 2-a] indeno [1, 2-e] acid pyrazine-1 -yl]} butyric, l-phenylacetyl-spirofpiperidine ^ lO'-δ'H.IO'H-imidazofl ^ -ajindénofl ^ -e] yrazine] -4'-one,
1-(méthylcarbamoyl)-spiro[pipéridine-4,10'-5Η,10Η-imidazo[1,2-a]indéno1- (methylcarbamoyl) -spiro [piperidine-4,10'-5Η, 10Η-imidazo [1,2-a] indéno
[1 ,2-e]pyrazine]-4'-one, 1-méthyl-spiro[pipéridine-4,10'-5Η,10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,[1, 2-e] pyrazine] -4'-one, 1-methyl-spiro [piperidine-4,10'-5Η, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
1-benzyl-spiro[pipéridine-4,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,1-benzyl-spiro [piperidine-4,10'-5'H, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
1-phénéthyl-spiro[pipéridine-4,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyra- zine]-4'-one,1-phenethyl-spiro [piperidine-4,10'-5Η, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-acétyl-spiro[pyrrolidine-2,10'-5'H,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-acetyl-spiro [pyrrolidine-2,10'-5'H, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-[(3-méthyluréido)acétyl]-spiro[pyrrolidine-2,10'-5'HJ0Η-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one, (10'RS)-1-(phénylcarbamoyl)-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1 - [(3-methylureido) acetyl] -spiro [pyrrolidine-2,10'-5'HJ0Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, (10'RS) -1- (phenylcarbamoyl) -spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] - 4'-one,
(10'RS)-1-méthyl-8'-fluoro-spiro[pyrrolidine-2,10'-5Η,10'H-imidazo[1,2-a] indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1-methyl-8'-fluoro-spiro [pyrrolidine-2,10'-5Η, 10'H-imidazo [1,2-a] indeno [1, 2-e] pyrazine] -4 '-one,
(10'RS)-1-éthyl-spiro[pyrrolidine-2J0'-5ΗJ0'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-ethyl-spiro [pyrrolidine-2J0'-5ΗJ0'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1 -propyl-spiro[pyrrolidine-2,10'-5'H,10'H-imidazo [1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1 -propyl-spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one ,
(10'RS)-4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pyrrolidine-2,10'-10'H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylate d'éthyle,(10'RS) -4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [pyrrolidine-2,10'-10'H-imidazo [1, 2- a] indéno [1 , 2-e] pyrazine-1 -yl]} - butyric, 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxamide,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxamide,
8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylate d'éthyle, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl azazine-2-carboxylate, acid 8- (3-methylureido) -4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
7-chloro-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxylate d'éthyle, acide 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide 10-(1 -pyrrolyle)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 2-carboxylique, acide 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylique, acide 7-chloro-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 8-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 5-(2-carboxy-10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno7-chloro-4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 4,5-dihydro acid -4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 10- (1 -pyrrolyl) -4,5-dihydro-4-oxo- 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 10-amino-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 2-carboxylic, 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic acid 7-chloro-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-2-carboxylic acid 8-amino-4,5- dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic, 5- (2-carboxy-10-methyl-4,5-dihydro-4- oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-10-yl)valérique, acide 4,5-dihydro-4, 10-dioxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide (E)-4,5-dihydro-4-oxo-10-(3-carboxybenzylidène)-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 10-(3-carboxypropionylamino)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 10-(3-phényluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-[(1 -méthylimidazol-2-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-2-yl)méthyl]-4,5-dihydro-4-oxo-10H-imidazo [1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 4-[10-(2-carboxy-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zinylidène)aminooxy]butyrique,[1, 2-e] pyrazine-10-yl) valeric, 4,5-dihydro-4, 10-dioxo-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxy- lique, acid (E) -4,5-dihydro-4-oxo-10- (3-carboxybenzylidene) -imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic acid 10- (3-carboxypropionylamino) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic, 10- (3-phenylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid, 10 - [(1 - methylimidazol-2-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol- 5-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-2- yl) methyl] -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-5- yl) methyl] -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 4- [10- (2-carboxy- 4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazinylidene) aminooxy] butyric,
8-fluoro-4-oxo-4,5-dihydro-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxylate d'éthyle, acide 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 4-oxo-10-[1 -(2-oxo-2,5-dihydropyrrolyl)]-4,5-dihydro-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)acé- tique,8-fluoro-4-oxo-4,5-dihydro-1 OH-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 8-fluoro-4 acid -oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 4-oxo-10- [1 - (2-oxo-2, 5-dihydropyrrolyl)] - 4,5-dihydro-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid (4,5-dihydro-4-oxo-10H- imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetic,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)méthyl] acétamide, 9-[(3-méthyluréido)méthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] acetamide, 9 - [(3-methylureido) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,N-methyl- [4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4 acid, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid,
8-(3-méthyluréido)méthyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo- acid 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) carboxamide,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carboxamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)carbonyl] glycine, N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno [1 ,2-e]pyrazine-2-carboxylique,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carbonyl] glycine, N-benzyl- (4,5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, acid 8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4- oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno [1 ,2- e]pyrazine-2-carboxylique, acide 8-(2-carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 9-[(3-méthyluréido)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-N-méthylaminocarbonylméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno-no [1, 2-e] ethyl pyrazine-2-carboxylate, acid 9- N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-2-carboxylic, 8- (2-carboxyethyl) acid -4.5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9 - [(3-methylureido) methyl] -4,5-dihydro-4 -oxo-10H-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic, 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 9-N-methylaminocarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-2-carboxylic acid 9- (1 -carboxyethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic,
9-(1H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-phosphonique, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique,9- (1H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 9- (1 H-tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic acid 9- (1 H-tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 2-phosphonic, 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic,
9-cyanométhyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 9-(4-phényl-1 H-imidazol-2-yl-méthyl)-4,5-dihydro-4-oxo-1 OH-imida- zo[1 ,2-a]indéno [1 ,2-e]pyrazine-2-carboxylique, acide 3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (E)-3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 9-benzènesulfonamidocarbonylméthyl-4-oxo-4,5-dihydro-1 OH-imidazo9-cyanomethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4-oxo-4,5-dihydro-10H-imidazo acid [1 , 2-a] indeno [1, 2-e] pyrazine-2-methylphosphonic acid 9- (4-phenyl-1 H-imidazol-2-yl-methyl) -4,5-dihydro-4-oxo -1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] pyrazin-2-yl) -propionic, acid (E) -3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-2-yl) -acrylic, 4-oxo-9-phosphonomethyl-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e ] pyrazine-2-carboxylic acid 2- (4-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9- acetic acid 2- (3-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, acid 2- (2 -carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 9-benzenesulfonamidocarbonylmethyl-4-oxo-4,5 -dihydro-1 OH-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-méthylsulfonamido-carbonylméthyl-4-oxo-4,5-dihydro-1 OH-imidazo[1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 9-methylsulfonamido-carbonylmethyl-4-oxo-4,5-dihydro-1 OH-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique,[1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,1,4-dihydro-5H-indeno [1,2-b] pyrazine-2,3-dione,
8-chloro-1 ,4-dihydro-5H-indeno[1 ,2-b]pyrazine-2,3-dione, acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5-yl)acéti- que, 5-amino-8-chloro-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, acid (5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-5-yl) acetic, 5-amino-8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione,
7-(3-phényluréido)-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,7- (3-phenylureido) -1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione,
(E)-5-carboxyméthylène-8-chloro-1 ,4-dihydro-indéno[1 ,2-b]pyrazine-2,3- dione, acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5- yl)acétique,(E) -5-carboxymethylene-8-chloro-1,4-dihydro-indeno [1,2-b] pyrazine-2,3-dione, acid (8-chloro-5-methyl-2,3-dioxo- 1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-5-yl) acetic,
(+) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1 H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(+) (5-methyl-2,3-dioxo-1, 4-dihydro-1 H-indeno [1,2-b] pyrazine-5-yl) acetic acid,
(-) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1 H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(-) (5-methyl-2,3-dioxo-1, 4-dihydro-1 H-indeno [1, 2-b] pyrazine-5-yl) acetic acid,
(+) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-(+) acid (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indéno [1, 2-b] pyrazine-
5-yl)acétique,5-yl) acetic,
(-) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-(-) acid (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indéno [1, 2-b] pyrazine-
5-yl)acétique acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1 (2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775),5-yl) acetic acid [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -quino-noxalinyl] methyl] phosphonic (ZK200775),
1 ,4-dihydro-6-(1 H-imidazol-1 -yl)-7-nitro-2,3-quinoxalinedione (YM 900 et1, 4-dihydro-6- (1 H-imidazol-1 -yl) -7-nitro-2,3-quinoxalinedione (YM 900 and
YM90K), acide 3,4-dihydro-7-(1 H-imidazol-1 -yl)-6-nitro-2,3-dioxo-1 (2H)-quinoxaline- acétique (YM 872),YM90K), 3,4-dihydro-7- (1 H-imidazol-1 -yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic acid (YM 872),
1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide
(NBQX),(NBQX),
1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),1, 4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),
1 ,2,3,4-tétrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX), 1-(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4-di- hydro-5H-2,3-benzodiazépine (LY 300168),1,2,3,4-tetrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX), 1- (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3 , 4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
4-(8-méthyl-9H-1 ,3-dioxolo[4,5-h][2,3]benzodiazépin-5-yl-benzénamine4- (8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepin-5-yl-benzenamine
(GYKI52466),(GYKI52466),
(-)-3-Acétyl-1-(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H- 2,3-benzodiazépine (LY 300164), le composé Ro48-8587, acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490) acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le composé SH608 leurs sels pharmaceutiquement acceptables et leurs énantiomères lorsqu'ils comportent un carbone asymétrique.(-) - 3-Acetyl-1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-2,3-benzodiazepine (LY 300164), the compound Ro48-8587, decahydro-6- [2- (1H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325), decahydro-6 acid - [2- (1H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic (LY 293558), decahydro-6- acid [2- (1H-tetrazol-5 -yl) ethyl] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490) (6,7-dichloro-1,2,2-dihydro-2-oxo-3-qinolinyl) phosphonic acid (S176252 ), the compound SH608, their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
9 - Utilisation selon l'une des revendications 1 à 3 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA est un antagoniste des récepteurs AMPA sélectif.9 - Use according to one of claims 1 to 3 for the preparation of a medicament for which the AMPA receptor antagonist is a selective AMPA receptor antagonist.
10 - Utilisation selon la revendication 9 pour la préparation d'un médicament pour lequel l'antagoniste des récepteurs AMPA sélectif est choisi parmi les composés suivants :10 - Use according to claim 9 for the preparation of a medicament for which the selective AMPA receptor antagonist is chosen from the following compounds:
10-acétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxyméthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4, 10-dione, 9-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-éthoxycarbonylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxymethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4, 10-dione, 9-phenylacetamido-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3 - (3-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one,
8-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-benzamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-benzylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(4-phénylbutyrylamino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(5-phénylvalérylamino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 8-(3,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3-(2-méthoxyphényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (4-phenylbutyrylamino-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 8- (5-phenylvalerylamino-5H, 10H-imidazo [1, 2- a] indeno [1,2-e] pyrazine-4-one, 8- (3,3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (2-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(4-méthylpentanoyl)amino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4 one,
8-(3-méthylthiouréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-éthoxycarbonyléthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one,8- [3- (2-ethoxycarbonylethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-[3-(3-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(3-éthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,8- [3- (2-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (3-ethylureido) -5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10-amino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-hydroxyimino-8-(3-méthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e] pyrazine-4-one, 8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4, 10-dione,10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4, 10-dione,
8-[3-morpholino-uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-thiouréido-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 8-(3-propyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-isopropyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-butyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[(2-thiazolin-2-yl)amino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3-morpholino-ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-thiouréido-5H, 10H-imidazo [1, 2- a] indeno [1,2-e] pyrazine-4-one, 8- (3-propylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-isopropylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-butylureido) -5H, 10H-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-4-one, 8 - [(2-thiazolin-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carbométhoxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one, 8-[3-(2-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carbomethoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (2-fluorobenzyl ) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carboxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(1 ,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3- (4-carboxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (1, 3-dimethylureido) -5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-carboxamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9-carboxamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-éthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)acé- tique,9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, acid (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetic,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)méthyl] acétamide, N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, 8-(3-méthyluréido)méthyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] acetamide, N-methyl- [4,5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4,5-dihydro-4-oxo- 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo- acid 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno [1 ,2-e]pyrazine-2-carboxylique,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, acid 8- (N-ethylaminocarbonylmethyl) - 4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 9-carboxymethyl acid 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 9- (1 -carboxyethyl) -4,5-dihydro-4 -oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
9-(1 H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-phosphonique, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (£)-3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyρhényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, 10-(1-carboxy-1-hydroxyméthyl)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyl]propionique,9- (1 H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one, acid 9- (1 H-tetrazole- 5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9- (1 H- tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 4,5-dihydro -4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic, 9-carboxymethyl-4-oxo-4,5-dihydro-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-2-methylphosphonic acid 3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [1, 2-a] indeno [ 1, 2-e] py- razin-2-yl) -propionic, acid (£) -3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2-a] indeno [1 , 2- e] pyrazine-2-yl) -acrylic, 4-oxo-9-phosphonomethyl-5, 10-dihydro-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2 -carboxylic acid 2- (4-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 2- (3-carboxyρhenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic acid, 2- (2-carboxyphenyl acid) ) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 10- (1-carboxy-1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid 3- [10- (4-oxo-4,5-dihydro-10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
10-(carboxyméthylène)-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno [1 ,2- e]pyrazine-4-one,10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique, 10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl]aminocarbonyl}propionique, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-2-carboxylique, acide (10'RS)-4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pyrrolidine-2,10'-10'H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid [8- (3-methylureido ) -4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, 10-amino-10-methyl-8- ( 3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (+) acid [8- (3-methylureido) -4,5-dihydro- 4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3-methylureido) -4,5-dihydro-4 -oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, 3- {10- [10-methyl-8- (3-methylureido) -4- acid oxo-4,5-dihydro-1 OH-imidazo [1,2-a] indeno [1,2-e] pyrazinyl] aminocarbonyl} propionic acid 8- (3-methylureido) -4,5-dihydro- 4-oxo-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-2-carboxylic acid (10'RS) -4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [pyrrolidine-2,10'-10'H-imidazo [1, 2-a] indéno [1, 2-e] pyrazine-1 -yl]} - butyric,
1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide
(NBQX), acide décahydro-6-[2-(1H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), 1 ,4-dihydro-6-(1H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione (YM 900 et(NBQX), decahydro-6- [2- (1H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558), 1,4-Dihydro-6- (1H-imidazol-1-yl) -7-nitro-2,3-quinoxalinedione (YM 900 and
YM90K), acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1(2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775), acide 3,4-dihydro-7-(1 H-imidazol-1 -yl)-6-nitro-2,3-dioxo-1 (2H)-quinoxaline- acétique (YM 872),YM90K), acid [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -qui- noxalinyl] methyl] phosphonic acid (ZK200775), acid 3 , 4-dihydro-7- (1 H-imidazol-1 -yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic (YM 872),
1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),1, 4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),
1 ,2,3,4-tétrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX),1,2,3,4-tetrahydro-7-nitro-2,3-dioxo-6-quinoxalinecarbonitrile (CNQX),
1-(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4- di- hydro-5H-2,3-benzodiazépine (LY 300168),1- (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
4-(8-méthyl-9H-1 ,3-dioxolo[4,5-h][2,3]benzodiazépin-5-yl-benzénamine4- (8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepin-5-yl-benzenamine
(GYKI52466),(GYKI52466),
(-)-3-Acétyl-1-(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H-(-) - 3-Acetyl-1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-
2,3-benzodiazépine (LY 300164), acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490), acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le composé Ro48-8587, le composé SH608 leurs sels pharmaceutiquement acceptables et leurs énantiomères lorsqu'ils contiennent un carbone asymétrique.2,3-benzodiazepine (LY 300164), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325) , decahydro-6- [2- (1H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558), decahydro-6- [2- ( 1H-tetrazol-5-yl) ethyl] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490), acid (6,7-dichloro-1, 2-dihydro-2-oxo-3 -qinolinyl) phosphonic (S176252), the compound Ro48-8587, the compound SH608 their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
11 - Utilisation du riluzole ou un de ses sels pharmaceutiquement acceptables et de l'acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-phosphonique ou un de ses sels pharmaceutiquement acceptables pour la préparation d'un médicament utile pour la prévention et/ou le traitement de la sclérose latérale amyotrophique. 12 - Association du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA à l'exception du CNQX et du GYKI52466.11 - Use of riluzole or one of its pharmaceutically acceptable salts and of 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo acid [1, 2- a] indeno [1, 2-e] pyrazine -2-phosphonic acid or a pharmaceutically acceptable salt thereof for the preparation of a medicament useful for the prevention and / or treatment of amyotrophic lateral sclerosis. 12 - Association of riluzole or one of its pharmaceutically acceptable salts and one or more AMPA receptor antagonists with the exception of CNQX and GYKI52466.
13 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-4-one de formule :13 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from 5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one derivatives of formula:
dans laquellein which
- R représente un radical N-alk, C(R4)R5, CH-Rg ou C=R7,- R represents an N-alk, C (R4) R5, CH-Rg or C = R7 radical,
- R-| et R2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux alkyle, alcoxy, amino, -N=CH-N(alk)alk', nitro, cyano, phényle, imidazolyle, SO3H, hydroxy, polyfluoroalcoxy, carboxy, alcoxycarbonyle, -NH-CO-NR11 R12, -N(alk)-CO-NR-| -| R-|2. -N(alk-Ar)-CO-NRι -|Ri2, -NH-CS-NR-11 R12, -N(alk)-CS-NR-| -| Ri2, -NH-CO-R-i 1 , -NH-CS-R24, -NH-C(=NR27)-NR1 QR12,- R- | and R2, identical or different, represent hydrogen or halogen atoms or alkyl, alkoxy, amino, -N = CH-N (alk) alk ', nitro, cyano, phenyl, imidazolyl, SO3H, hydroxy, polyfluoroalkoxy, carboxy, alkoxycarbonyl, -NH-CO-NR11 R12, -N (alk) -CO-NR- | - | R- | 2. -N (alk-Ar) -CO-NRι - | Ri2, -NH-CS-NR-11 R12, -N (alk) -CS-NR- | - | Ri2, -NH-CO-Ri 1, -NH-CS-R24, -NH-C (= NR 2 7) -NR 1 QR 1 2,
-N(alk)-C(=NR27)-NR1QR12, -CO-NR10R-|2, -NH-SO2-NR10R12.-N (alk) -C (= NR 2 7) -NR 1 QR 1 2, -CO-NR 10 R- | 2, -NH-SO2-NR10R12.
-N(alk)-Sθ2-NR10R-|2, -NH-S02-CF3, -NH-S02-alk, -NR10R-|3, -S(0)m-alk-Ar, -SO2-NR10R12, 2-oxo-1-imidazolidinyle dont la position -3 est éventuellement substituée par un radical alkyle ou 2-OXO-1 -perhydropyrimidinyle dont la position -3 est éventuellement substituée par un radical alkyle, - R3 représente un atome d'hydrogène ou un radical carboxy, alcoxycarbonyle ou carboxamido,-N (alk) -Sθ2-NR 10 R- | 2, -NH-S0 2 -CF 3 , -NH-S02-alk, -NR 10 R- | 3 , -S (0) m -alk-Ar, -SO2-NR10R12, 2-oxo-1-imidazolidinyl whose position -3 is optionally substituted by an alkyl radical or 2-OXO-1 -perhydropyrimidinyl whose position -3 is optionally substituted by an alkyl radical, - R3 represents a hydrogen atom or a carboxy, alkoxycarbonyl or carboxamido radical,
- R4 représente un radical alkyle, -alk-Het ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choi- sis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 et -alk-COOR-|Q,- R4 represents an alkyl, -alk-Het or phenylalkyl radical, the phenyl nucleus of which is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano radicals, - alk-NH2, -COOR10 and -alk-COOR- | Q,
- R5 représente un radical alkyle (1-11C en chaîne droite ou ramifiée), -alk-Het, -NR8Rg, -NH-CHO, -NH-COOR17, -NH-S0 R24, -COOR10, -alk-COOR-iQ, -alk-CONR^R-18, -alk-NR-|QRi8, -alk-OH, -alk-CN, phénylal- kyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-JQ et -alk-COOR-|o, -NH-CO-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-10 et -alk-COOR-|Q, -NH-CO-Het, -NH-CO-alk-Het, -NH-CO-alk-COOR10, -NH-CO-alk-NR108, -NH-CO-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-| Q et -alk-COOR-io, pyrrol-1-yle éventuellement substitué par un radical -COOR10, -NH-CO-NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q et -alk-COOR-|Q, -NH-CO-NH-Het, -NH-CO-NH-alk-Het, -NH-CO-NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 et -alk-COOR-jo, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH-alk ou -NH-CO-NH2, ou bien R4 et R5 forment ensemble avec l'atome de carbone auquel ils sont rattachés (a) un cycle 2- ou 3-pyrrolidine, un cycle 2- ou 4-pipéridine ou un cycle 2-azacycloheptane, ces cycles étant éventuellement substitués sur l'azote par un radical alkyle, -CHO, -COOR-| -| , -CO-alk-COORg, -CO-alk-NRgR-12, -CO-alk-CONRgRg, -CO-COORg,- R5 represents an alkyl radical (1-11C in a straight or branched chain), -alk-Het, -NR 8 Rg, -NH-CHO, -NH-COOR 17 , -NH-S0 R24, -COOR 10 , -alk -COOR-iQ, -alk-CONR ^ R-18, -alk-NR- | QRi8, -alk-OH, -alk-CN, phenylalkyl, the phenyl ring of which is optionally substituted by one or more substituents chosen from halogen atoms and the alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-JQ and -alk-COOR- | o, -NH-CO-Ar radicals in which Ar is optionally substituted by a or several substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-10 and -alk-COOR- | Q, -NH-CO-Het radicals, -NH-CO-alk-Het, -NH-CO-alk-COOR 10 , -NH-CO-alk-NR 108 , -NH-CO-alk-Ar whose Ar is optionally substituted by one or more selected substituents from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR- radicals | Q and -alk-COOR-io, pyrrol-1-yl optionally substituted by a radical -COOR10, -NH-CO-NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-I Q and -alk-COOR- | Q, -NH-CO-NH-Het, -NH-CO-NH-alk radicals -Het, -NH-CO-NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 radicals and -alk-COOR-jo, -NH-COalk, -NH-COcycloalkyle, -NH-CO-NH-alk or -NH-CO-NH 2 , or else R4 and R5 form together with the carbon atom to which they are attached (a) a 2- or 3-pyrrolidine ring, a 2- or 4-piperidine ring or a 2-azacycloheptane ring, these rings being optionally substituted on nitrogen via an alkyl radical, -CHO, -COOR- | - | , -CO-alk-COORg, -CO-alk-NRgR-12, -CO-alk-CONRgRg, -CO-COORg,
-CO-CH2-0-CH2-COORg, -CO-CH2-S-CH2-COORg, -CO-CH=CH-COORg, -CO-alk, -CO-Ar", -CO-alk-Ar", -CO-NH-Ar", -CO-NH-alk-Ar", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH2, -CO-NH-alk, -CO-N(alk)alk', -CS-NH2, -CS-NH-alk, -CS-NH-Ar", -CS-NH-Het, -alk-Het, -alk-NRgRg, -alk-COORg, -alk-CO-NRgRβ, -alk-Ar", -Sθ2-alk, -Sθ2-Ar ou -CO-cycloalkyle dont le cycloalkyle est éventuellement substitué en -2 par un radical carboxy, (b) un cycle 2-pyrrolidine-5-one ou (c) un cycloalkyle,-CO-CH 2 -0-CH2-COORg, -CO-CH 2 -S-CH 2 -COORg, -CO-CH = CH-COORg, -CO-alk, -CO-Ar ", -CO-alk- Ar ", -CO-NH-Ar", -CO-NH-alk-Ar ", -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, - CO-NH 2 , -CO-NH-alk, -CO-N (alk) alk ', -CS-NH 2 , -CS-NH-alk, -CS-NH-Ar ", -CS-NH-Het, -alk-Het, -alk-NRgRg, -alk-COORg, -alk-CO-NRgRβ, -alk-Ar ", -Sθ2-alk, -Sθ2-Ar or -CO-cycloalkyle the cycloalkyl of which is optionally substituted in - 2 by a carboxy radical, (b) a 2-pyrrolidine-5-one ring or (c) a cycloalkyl,
- Rg représente un atome d'hydrogène ou un radical hydroxy, alkyle (1-11C en chaîne droite ou ramifiée), -alk-OH, -NR-|4R-|5, -alk-NR-|4Ri5, -alk-Het, -NH-CHO, -COOalk, -alk-COOR-jo, -a!k-CO-NR-|oR2i , phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR-|o et -alk-COOR-|o, -R-|g-COOR-|Q, -CO-COOR-io, pyrrol-1-yle éventuellement substitué par un radical -COOR-| Q OU 2-oxo-2,5-dihydropyrrol-1 -yle,- Rg represents a hydrogen atom or a hydroxy radical, alkyl (1-11C in straight or branched chain), -alk-OH, -NR- | 4R- | 5, -alk-NR- | 4Ri5, -alk- Het, -NH-CHO, -COOalk, -alk-COOR-jo, -a! K-CO-NR- | oR2i, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR- | o and -alk-COOR- | o, -R- | g-COOR- | Q, -CO-COOR-io radicals , pyrrol-1-yl optionally substituted by a radical -COOR- | Q OR 2-oxo-2,5-dihydropyrrol-1 -yle,
- R7 représente un atome d'oxygène ou un radical NOH, NO-alk-COOR-io, NO-alk, CHR-jg, NR-|Q, C(COOR-|Q)R20 OU C(CONR1QR2I)R20-- R7 represents an oxygen atom or a NOH, NO-alk-COOR-io, NO-alk, CHR-jg, NR- | Q, C (COOR- | Q) R20 OR C (CONR 1 QR2I) R20 radical -
- Rδ représente un atome d'hydrogène ou un radical alkyle, -alk-COOR-|o, -alk-NRιoR2i , -alk-Het ou phénylalkyle dont le noyau phényle est éventuel- lement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 et -alk-COOR-io,- Rδ represents a hydrogen atom or an alkyl, -alk-COOR- | o, -alk-NRιoR2i, -alk-Het or phenylalkyl radical, the phenyl nucleus of which is optionally substituted by one or more substituents chosen from atoms halogen and the alkyl, alkoxy, nitro, amino, hydroxy, cyano, -alk-NH2, -COOR10 and -alk-COOR-io radicals,
- Rg représente un atome d'hydrogène ou un radical alkyle, - R-| Q représente un atome d'hydrogène ou un radical alkyle,- Rg represents a hydrogen atom or an alkyl radical, - R- | Q represents a hydrogen atom or an alkyl radical,
- R-| -j représente un atome d'hydrogène ou un radical alkyle (1-9C en chaîne droite ou ramifiée), -alk-COOR-io, -alk-Het, -alk-NR-|2Rιo, phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substi- tuants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-|Q, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alcoxycarbonyle, cyano et -alk-COOR-io ou -Het,- R- | -j represents a hydrogen atom or an alkyl radical (1-9C in a straight or branched chain), -alk-COOR-io, -alk-Het, -alk-NR- | 2Rιo, phenylalkyl of which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR- | Q, phenyl optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, carboxy, alkoxycarbonyl, cyano and -alk-COOR-io or -Het radicals,
- R-|2 représente un atome d'hydrogène ou un radical alkyle,- R- | 2 represents a hydrogen atom or an alkyl radical,
- R-|3 représente un radical alkyle, Het ou alcoxycarbonyle,- R- | 3 represents an alkyl, Het or alkoxycarbonyl radical,
- R-14 et R-|5, identiques ou différents représentent chacun un radical alkyle ou bien R14 représente un atome d'hydrogène et R15 représente un atome d'hydrogène ou un radical alkyle, -COR22, -CSR23 ou -SO2R24.- R-14 and R- | 5, identical or different, each represent an alkyl radical or else R14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl radical, -COR22, -CSR23 or -SO2R24.
- R-|g représente une chaîne -CHOH- ou -CH(OH)-alk(1-5C)-,- R- | g represents a chain -CHOH- or -CH (OH) -alk (1-5C) -,
- R-17 représente un radical alkyle ou phénylalkyle,- R-17 represents an alkyl or phenylalkyl radical,
- R-|8 représente un atome d'hydrogène ou un radical alkyle,- R- | 8 represents a hydrogen atom or an alkyl radical,
- R-jg représente un radical hydroxy, alkyle, -alk-Het, -NR2δR26> -alk-COOR-iQ, -Het, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-JQ, cyano et -alk-COOR-jQ ou phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-JO, cyano et - R20 représente un atome d'hydrogène ou un radical alkyle,- R-jg represents a hydroxy, alkyl, -alk-Het, -NR2δR26> -alk-COOR-iQ, -Het, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy radicals , nitro, amino, hydroxy, -alk-NH2, -COOR-JQ, cyano and -alk-COOR-jQ or phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl radicals , alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-JO, cyano and - R20 represents a hydrogen atom or an alkyl radical,
- R21 représente un atome d'hydrogène ou un radical alkyle,- R21 represents a hydrogen atom or an alkyl radical,
- R22 représente un radical alkyle, cycloalkyle, -COOalk, -alk-COOR-|Q, phényle éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-| Q, cyano et -alk-COOR-|o, phénylalkyle dont le noyau phényle est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR10, cyano et -alk-COOR-|Q, -alk-NRιoRi2, -NH-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR10, cyano et -alk-COOR-jo, -Het, -alk-Het, -OR-17, -NH-alk-Ar dont Ar est éventuellement substitué par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux alkyle, alcoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano et -alk-COOR-io, -NH-alk-Het, -NH-alk, -NH2 ou -NH-Het,- R22 represents an alkyl, cycloalkyl, -COOalk, -alk-COOR- | Q, phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk radicals -NH2, -COOR- | Q, cyano and -alk-COOR- | o, phenylalkyl in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2 radicals, -COOR10, cyano and -alk-COOR- | Q, -alk-NRιoRi2, -NH-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino radicals, hydroxy, -alk-NH2, -COOR10, cyano and -alk-COOR-jo, -Het, -alk-Het, -OR-17, -NH-alk-Ar in which Ar is optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, nitro, amino, hydroxy, -alk-NH2, -COOR-I Q, cyano and -alk-COOR-io, -NH-alk-Het, -NH-alk radicals, -NH 2 or -NH-Het,
- R23 représente un radical -NH-alk, -NH-Ar, -NH-Het ou -NH2,- R23 represents a radical -NH-alk, -NH-Ar, -NH-Het or -NH2,
- R24 représente un radical alkyle ou phényle,- R24 represents an alkyl or phenyl radical,
- R25 et R26- identiques ou différents, représentent chacun un radical alkyle ou cycloalkyle,- R25 and R 26- identical or different, each represent an alkyl or cycloalkyl radical,
- R27 représente un atome d'hydrogène ou un radical alkyle,- R27 represents a hydrogen atom or an alkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
- alk' représente un radical alkyle,- alk 'represents an alkyl radical,
- m est égal à 0, 1 ou 2, - Ar représente un radical phényle,- m is equal to 0, 1 or 2, - Ar represents a phenyl radical,
- Het représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes (O, S, N) éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle,Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms (O, S, N) optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals,
les radicaux et portions alkyle, alkylène et alcoxy contiennent 1 à 6 atomes de carbone et sont en chaîne droite ou ramifiée, les radicaux et portions acyle contiennent 2 à 4 atomes de carbone, les radicaux cycloalkyle contiennent 3 à 6 atomes de carbone et les atomes d'halogène sont choisis parmi le fluor, le chlore, le brome et l'iode,alkyl, alkylene and alkoxy radicals and portions contain 1 to 6 carbon atoms and are in a straight or branched chain, acyl radicals and portions contain 2 to 4 carbon atoms, cycloalkyl radicals contain 3 to 6 carbon atoms and the atoms of halogen are chosen from fluorine, chlorine, bromine and iodine,
les isomères (E et Z) et leurs mélanges des composés pour lesquels R7 représente un radical NO-alk, C(COOR-|o)R20. C(CONRI QR21 )R20 OU CHR-jg, les formes tautomères (E et Z) des composés pour lesquels R représente un radical CH-Rg et Rg représente un radical -CO-COOR-I Q, les énantiomères et diastéreoisomeres des composés pour lesquels R représente un radical C(R4)R5 ou CH-Rgthe isomers (E and Z) and their mixtures of the compounds for which R7 represents a radical NO-alk, C (COOR- | o) R20. C (CONRI QR21) R20 OR CHR-jg, the tautomeric forms (E and Z) of the compounds for which R represents a radical CH-Rg and Rg represents a radical -CO-COOR-I Q, the enantiomers and diastereoisomers of the compounds for which R represents a radical C (R4) R5 or CH-Rg
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
14 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-4-one de formule :14 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from 5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one derivatives of formula:
dans laquelle, in which,
- R' représente un atome d'hydrogène ou un radical carboxy, alcoxycarbonyle, -CO-NR'4R'5) -PO3H2 ou -CH2OH,- R 'represents a hydrogen atom or a carboxy, alkoxycarbonyl, -CO-NR'4R' 5) -PO3H2 or -CH 2 OH radical,
- R'-| représente un radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR'5R'g ou -CO-NH-R'7,- R'- | represents a radical -alk-NH2, -alk-NH-CO-R'3, -alk-COOR'4, -alk-CO-NR ' 5 R'g or -CO-NH-R'7,
- R'3 représente un radical alkyle, phényle, phénylalkyle, cycloalkyle ou -NR'gR's,- R'3 represents an alkyl, phenyl, phenylalkyl, cycloalkyl or -NR'gR's radical,
- R'4 représente un atome d'hydrogène ou un radical alkyle,- R'4 represents a hydrogen atom or an alkyl radical,
- R'5 représente un atome d'hydrogène ou un radical alkyle, phényle, cycloal- kyle ou phénylalkyle,R'5 represents a hydrogen atom or an alkyl, phenyl, cycloalkyl or phenylalkyl radical,
- R'g représente un atome d'hydrogène ou un radical alkyle,- R'g represents a hydrogen atom or an alkyl radical,
ou bien R'5 et R'g forment avec l'atome d'azote auquel ils sont rattachés un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 6 atomes de carbone et éventuellement un ou plusieurs autres hétéroatomes choisis parmi O, S, N,or else R'5 and R'g form, with the nitrogen atom to which they are attached, a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 6 carbon atoms and optionally one or more other heteroatoms chosen from O, S, N ,
- R'7 représente un radical phényle, phénylalkyle ou -alk-COOR'4,- R'7 represents a phenyl, phenylalkyl or -alk-COOR'4 radical,
- R'g représente un atome d'hydrogène ou un radical alkyle, cycloalkyle ou phénylalkyle,R'g represents a hydrogen atom or an alkyl, cycloalkyl or phenylalkyl radical,
- alk représente un radical alkyle ou alkylène,alk represents an alkyl or alkylene radical,
les radicaux et portions alcoxy, alkyle et alkylène contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée et les radicaux cycloalkyle contiennant 3 à 6 atomes de carbone leurs énantiomères et stéréoisomères et leurs sels pharmaceutiquement acceptables.alkoxy, alkyl and alkylene radicals and portions containing 1 to 6 carbon atoms in a straight or branched chain and cycloalkyl radicals containing 3 to 6 carbon atoms their enantiomers and stereoisomers and their pharmaceutically acceptable salts.
15 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de 5H,10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-4-one de formule :15 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from derivatives of 5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one of formula:
dans laquellein which
R" représente un atome d'hydrogène ou un radical -COOH, -alk-COOH, -PO3H2, -CH2-PO3H2, -CH=CH-COOH ou phényle substitué par un radical carboxy,R "represents a hydrogen atom or a radical -COOH, -alk-COOH, -PO3H2, -CH2-PO3H2, -CH = CH-COOH or phenyl substituted by a carboxy radical,
R"1 représente un radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H2 ou -alk-C0-NH-S02R"2.R "1 represents a radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H2 or -alk-C0-NH-S02R" 2.
R"2 représente un radical alkyle ou phényle,R "2 represents an alkyl or phenyl radical,
alk représente un radical alkyle,alk represents an alkyl radical,
Het représente un hétérocycle mono ou polycyclique saturé ou insaturé contenant 1 à 9 atomes de carbone et un ou plusieurs hétéroatomes choisis parmi O, S, N, l'hétérocycle étant éventuellement substitué par un ou plusieurs radicaux alkyle, phényle ou phénylalkyle, les radicaux alkyle et alcoxy contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée,Het represents a saturated or unsaturated mono or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms chosen from O, S, N, the heterocycle being optionally substituted by one or more alkyl, phenyl or phenylalkyl radicals, alkyl and alkoxy radicals containing 1 to 6 carbon atoms in a straight or branched chain,
les isomères (E et Z) des composés pour lesquels R représente un radical -CH=CH-COOH, les racémiques, énantiomères et diastéreoisomeres des composés pour lesquels R représente un radical -alk-COOH et/ou R, représente un radical -alk-CN, -alk-COOH, -alk-Het, -alk-P03H2 ou -alk-C0-NH-S02R2the isomers (E and Z) of the compounds for which R represents a radical -CH = CH-COOH, the racemates, enantiomers and diastereoisomers of the compounds for which R represents a radical -alk-COOH and / or R represents a radical -alk -CN, -alk-COOH, -alk-Het, -alk-P03H2 or -alk-C0-NH-S02R2
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
16 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les dérivés de pyrazine-2,3-dione de formule :16 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from pyrazine-2,3-dione derivatives of formula:
dans laquellein which
- R"' représente un radical C(R"'4)R'"5, CH-R'"6 ou C=R'"7,- R "'represents a radical C (R"' 4) R '" 5 , CH-R'" 6 or C = R '" 7 ,
- R'"ι et R'"2, identiques ou différents, représentent des atomes d'hydrogène ou d'halogène ou des radicaux amino, nitro ou -NH-CO-NR"'ι 1 R"'-|2,- R '"ι and R'" 2, identical or different, represent hydrogen or halogen atoms or amino, nitro or -NH-CO-NR "" ι 1 R "'- | 2,
- R'"3 représente un atome d'oxygène,- R '"3 represents an oxygen atom,
- R'"4 représente un radical alkyle,- R '"4 represents an alkyl radical,
- R'"5 représente un radical -alk-COOR"'ιo>- R '"5 represents a radical -alk-COOR"' ιo>
- R"'g représente un atome d'hydrogène ou un radical -NR"'-|4R"'-|5, - R'"7 représente un radical NOH ou C(COOR"'ιo)R"'2θ.- R "'g represents a hydrogen atom or a radical -NR"' - | 4R "'- | 5, - R '"7 represents a NOH or C (COOR"' ιo) R "'2θ radical.
- R"'-|o représente un atome d'hydrogène ou un radical alkyle,- R "'- | o represents a hydrogen atom or an alkyl radical,
- R"'-| -| représente phényle,- R "'- | - | represents phenyl,
- R"'-|2 représente un atome d'hydrogène,- R "'- | 2 represents a hydrogen atom,
- R"'-|4 représente un atome d'hydrogène,- R "'- | 4 represents a hydrogen atom,
- R'"i5 représente un atome d'hydrogène ou un radical -COR'"22.- R '"i5 represents a hydrogen atom or a radical -COR'" 22.
- R'"20 représente un atome d'hydrogène,- R '"20 represents a hydrogen atom,
- R"'22 représente un radical alkyle,- R "'22 represents an alkyl radical,
- alk représente un radical alkyle,- alk represents an alkyl radical,
les radicaux et portions alkyle contiennant 1 à 6 atomes de carbone en chaîne droite ou ramifiée et les atomes d'halogène étant choisis parmi le fluor, le chlore, le brome et l'iode,the radicals and alkyl portions containing 1 to 6 carbon atoms in a straight or branched chain and the halogen atoms being chosen from fluorine, chlorine, bromine and iodine,
les isomères (E et Z) des composés pour lesquels R'" représente un radical C=R'"7 et R'"7 représente un radical C(COOR"'ιo)R'"20' les énantiomères et diastéreoisomeres des composés de formule (I) pour lesquels R représente un radical C(R4)R5 ou CH-Rg,the isomers (E and Z) of the compounds for which R '"represents a radical C = R'" 7 and R '"7 represents a radical C (COOR"' ιo) R '"20' the enantiomers and diastereoisomers of the compounds of formula (I) for which R represents a radical C (R4) R5 or CH-Rg,
et leurs sels pharmaceutiquement acceptables.and their pharmaceutically acceptable salts.
17 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les composés suivants :17 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from the following compounds:
8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 8-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-chloro-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-phényl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(1 -imidazolyl)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 4-oxo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-sulfonique, 7-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-bromo-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 6,7-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,8-dichloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8,9-dichloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7,9-dichloro-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-nitro 9-bromo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5HJ 0H-8-méthoxy-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-amino-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-(3-phényluréido)-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-acétamido-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H,10H-8-diméthylaminométhylèneamino-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 9-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-chloro-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 9-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-phenyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (1 -imidazolyl) -5HJ 0H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4 -one, 4-oxo-5H acid, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-sulfonic, 7-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-bromo-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 6,7-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7,8-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8.9-dichloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7.9- dichloro-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-nitro 9-bromo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5HJ 0H-8-methoxy-imidazo [1, 2-a] i ndeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-amino-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8- (3-phenylureido) -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-8-acetamido-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 5H, 10H-8-dimethylaminomethyleneamino-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
7-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxy-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 10-acétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,7-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxy-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-5H, 10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(E-diméthylaminométhylène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine10- (E-dimethylaminomethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine
-4-one,-4-one,
10-hydroxyméthylène-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-hydroxymethylene-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10J0-diméthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10:1'-cyclopropane]-4-one, spiro[5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10:1'-cyclopentane]-4-one,10J0-dimethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-10: 1'-cyclopropane] -4-one, spiro [5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10: 1'-cyclopentane] -4-one,
10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-hydroxyméthyl-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-hydroxymethyl-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(2-furylméthyl)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-pyridylméthylène)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-pyridylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(phénylpropyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-pyridylméthylène)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 10-(3-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyridylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-imidazolylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide (4-oxo-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)amino- oxyacétique, 10-propionamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-isobutyramido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-7-chloro-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzènesulfonylamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10- (2-furylmethyl) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-pyridylmethylene) -5H, 10H-imidazo [1, 2 -a] indeno [1, 2-e] pyrazine-4-one, 10- (4-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one , 10- (phenylpropyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-pyridylmethylene) -5H, 10H-imidazo [1, 2 -a] indeno [1,2-e] pyrazine-4-one, 10- (3-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one , 10- (2-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-imidazolylmethyl) -5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one, 10-isobutyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid (4-oxo-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-ylidene) amino-oxyacetic, 10-propionamido-5H, 10H-imidazo [1, 2-a ] indeno [1, 2-e] pyrazine-4-one, 10-amino-8-fluoro-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-isobutyramido-5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-7-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2 -e] pyrazine-4-one, 10-benzenesulfonylamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4 one,
10-méthylamino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-pyrazinylméthylène)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-(2-pyrazinylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-méthylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-méthyl-10-(4-pyridylméthyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 10-(4-pipéridylméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-benzyl-7-chloro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione, 10-(3-phényluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 7-chloro-10-(3-phényluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10-methylamino-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-pyrazinylmethylene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10- (2-pyrazinylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 7-chloro-10-methylamino-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 10-methyl-10- (4-pyridylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one, 10- (4-piperidylmethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-benzyl-7-chloro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4,10-dione, 10- (3-phenylureido) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 7-chloro- 10- (3-phenylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-méthyl-10-[2-(pyridine-4-yl)éthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] py- razine-4-one,10-methyl-10- [2- (pyridine-4-yl) ethyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-éthoxycarbonylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-cyanophényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,9-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-cyanophenyl) ureido] -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-méthoxyphényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one, 8-phénylacétamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-tert-butyluréido)-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one, 8-phenylacetamido-5H, 10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4 -one, 8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-benzylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-tert-butylureido) -5HJ0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-benzamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(4-phénylbutyrylamino-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 8-(5-phénylvalérylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-éthoxycarbonylméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyra- zine-4-one,8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (4-phenylbutyrylamino-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 8- (5-phenylvalerylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3 -ethoxycarbonylmethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-(3-carboxyméthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (3-carboxymethylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4- one,
8-(3,3-diméthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3,3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-hydroxy-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-aminopropionamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-aminoacétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-hydroxy-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-aminopropionamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8-aminoacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-nitrophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-nitrophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,8- [3- (2-methoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4-one,
8-[3-(2-nitrophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-nitrophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-aminophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-méthoxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- [3- (4-aminophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-methoxyphenyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
8-(4-méthylpentanoyl)amino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4 one,
N,N-diméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8- sulfonamide,N, N-dimethyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-sulfonamide,
8-(3-phénylthiouréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-phenylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-méthylthiouréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(2-oxo-1 -imidazolinyl)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (2-oxo-1 -imidazolinyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-formamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-éthoxycarbonylpropionylamino)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]py- razine-4-one,8-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-ethoxycarbonylpropionylamino) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-éthoxycarbonyléthyl)uréido]-5HJ0H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one,8- [3- (2-ethoxycarbonylethyl) ureido] -5HJOH-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-[3-(2-carboxyéthyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-carboxyethyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(2-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (2-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(3-éthyluréido)-5HJ 0H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,8- (3-ethylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-morpholino-uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3-morpholino-ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-8- (3-methylureido) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one,
10-hydroxyimino-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4, 10-dione, 8-[3-(3-aminophényl)uréido]-5H,10H-imidazo[1 ,2-a]indénô[1,2-e]pyrazine-4- one, acide 5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one-8-carboxylique,8- (3-methylureido) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4, 10-dione, 8- [3- (3-aminophenyl) ureido] -5H, 10H -imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one, 5H, 10H acid-imidazo [1,2-a] indeno [1,2, e] pyrazine-4-one- 8-carboxylic,
8-uréido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-ureido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(2-aminoéthyl)thiouréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-aminoethyl) thioureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-thiouréido-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,8-thiouréido-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-imidazoline-2-yl)amino]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8 - [(2-imidazoline-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[(1 -pyrrolidinyl)carbonylamino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazi- ne-4-one,8 - [(1 -pyrrolidinyl) carbonylamino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(1 -azétidinyl)carbonylamino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazi-ne-8 - [(1 -azetidinyl) carbonylamino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazi-ne-
4-one,4-one,
8-(3-propyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one,8- (3-propylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
8-(3-isopropyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, 8-(3-butyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-isopropylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 8- (3-butylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-thiazolin-2-yl)amino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8 - [(2-thiazolin-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-(1 ,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (1, 3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-carbométhoxyphényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one, 8-[3-(3-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carbomethoxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-[3-(4-carbométhoxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-4-one,8- [3- (4-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- [3- (4-carbomethoxybenzyl) ureido ] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(4-carboxybenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carboxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorobenzyl)uréido]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (2-fluorobenzyl) ureido] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-fluorobenzyl)uréido]-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 9-carboxy-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3- (4-fluorobenzyl) ureido] -5HJ0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 9-carboxy-5H, 10H-imidazo [1,2 -a] indeno [1, 2-e] pyrazine-4-one,
9-carboxamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9-carboxamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-diéthylcarboxamido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9- (N-diethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-éthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
9-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(4-méthoxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (4-methoxybenzyl) ureido] -5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one,4-one,
8-méthylsulfonamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-methylsulfonamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
5HJ0H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one-10-carboxylate d'éthyle,5HJOH-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one-10-ethyl carboxylate,
10-imino-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-imino-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(4-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (4-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-carboxybenzylidène)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,10- (3-carboxybenzylidene) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
10-(3-carboxybenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(4-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-[(1 -méthylimidazol-2-yl)méthylène]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one,10- (3-carboxybenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (4-aminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10 - [(1-methylimidazol-2-yl) methylene] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(carboxyméthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (carboxymethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(carboxyméthylène)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 5-(4-hydroxy-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-ylidène)penta- noïque,10- (carboxymethylene) -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, acid 5- (4-hydroxy-imidazo [1,2-a] indeno [ 1, 2-e] pyrazine-10-ylidene) pentanoic,
10-(1-carboxy-1-hydroxyméthyl)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,10- (1-carboxy-1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-nicotinoylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 3-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-è]pyrazinyl)amino- carbonyl]propionate de méthyle,10-nicotinoylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 3- [10- (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-è] pyrazinyl) amino-carbonyl] methyl propionate,
10-(3-diéthylaminopropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,10- (3-diethylaminopropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-formamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, (10R)-10[(R)-α-méthoxy-α-trifluorométhylphénylacétamido]-5H,10H-imida- zo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-formamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (10R) -10 [(R) -α-methoxy-α-trifluoromethylphenylacetamido] -5H , 10H-imida- zo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
(10S)-10[(R)-α-méthoxy-α-trifluorométhylphénylacétamido]-5H,10H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,(10S) -10 [(R) -α-methoxy-α-trifluoromethylphenylacetamido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-phénylacétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, N-[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]carba- mate de tert-butyle,10-phenylacetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, N- [10- (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazinyl)] tert-butyl carbamate,
10-(1-pyrrolyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (1-pyrrolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
1 -[10-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)]pyrrole-2- carboxylate de méthyle, 10-méthoxyimino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,1 - [10- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] methyl pyrrole-2-carboxylate, 10-methoxyimino-5H , 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-acétamido-10-méthyl-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10-acetamido-10-methyl-5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(4-imidazolylméthyl)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (4-imidazolylmethyl) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 10-(carboxyméthylène)-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-n-propyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one, 10-(3-aminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-methyl-8- (3-n-propylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one, 10- (3-aminobenzyl ) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-aminobenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10- (3-aminobenzylidene) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-(3-acétylaminobenzyl)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one,10- (3-acetylaminobenzyl) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one,
10-(3-méthoxycarbonylbenzylidène)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- (3-methoxycarbonylbenzylidene) -5H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
4-one, 10-amino-10-(3-phénylpropyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 5-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-10-yl)valérique,4-one, 10-amino-10- (3-phenylpropyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 5- (10-methyl- 4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-10-yl) valeric,
4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyrazine-10- yl)butyronitrile, acide 4-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)butyrique,4- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyronitrile, acid 4- (10- methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) butyric,
10-hydroxyméthyl-10-méthyl-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one, acide (10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)acétique,10-hydroxymethyl-10-methyl-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one, acid (10-methyl-4,5-dihydro-4-oxo- 10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) acetic,
3-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10- yl)propionitrile, acide 3-(10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2,-a]indéno[1 ,2-e]pyra- zine-10-yl)propionique,3- (10-methyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl) propionitrile, acid 3- (10-methyl -4,5-dihydro-4-oxo-10H-imidazo [1, 2, -a] indeno [1, 2-e] pyrazine-10-yl) propionic,
10-méthyl-10-[(1-méthylimidazol-2-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno10-methyl-10 - [(1-methylimidazol-2-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-4-one,[1, 2-e] pyrazine-4-one,
10-[(1 -méthylimidazol-5-yl)méthylène]-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, 10-[(1 -méthylimidazol-5-yl)méthyl]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-4-one,10 - [(1-methylimidazol-5-yl) methylene] -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10 - [(1-methylimidazol-5-yl) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[3-(3-fluorophényl)uréido]-10-(carboxyméthyl)-5H,10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno8- [3- (3-fluorophenyl) ureido] -10- (carboxymethyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid [8 - (3-methyluréido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (+) [8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno [1 ,2-e]pyrazine-10-yl]acétique, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-10-yl) gly- colique,[1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3-methyluréido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indéno [ 1, 2-e] pyrazine-10-yl] acetic, acid (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl) glycolic,
10-méthyl-10-(1 -pyrrolyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 1 -[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl)] pyrrole-2-carboxylique, acide 3-[10-(4-oxo-4,5-dihydro-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyl]propionique,10-methyl-10- (1 -pyrrolyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid 1 - [10- (4-oxo-4 , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl)] pyrrole-2-carboxylic acid 3- [10- (4-oxo-4,5-dihydro-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
10-amino-10-éthyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-ethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-benzyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-10-propyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]propionique,10-amino-10-benzyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-10-propyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid 3- [10- (10-methyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] propionic,
N-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indéno[1 ,2-e]pyra- zinyl)]carbamate de tert-butyle, acide 4-[10-(10-méthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazinyl)aminocarbonyl]butyrique,N- [10- (10-methyl-4-oxo-4,5-dihydro-10H-imidazo [1,2-a] indeno [1,2-e] pyrazinyl)] tert-butyl carbamate, acid 4- [10- (10-methyl-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] butyric,
10-amino-10-isopropyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-isopropyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-10-butyl-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-amino-10-butyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-méthyl-10-méthylamino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 10-amino-10-méthyl-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-4-one et ses énantiomères,10-methyl-10-methylamino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-4-one and its enantiomers,
10-(1 ,3-diméthyl-1 H-pyrazole-4-méthylène)-5H,10H-imidazo[1,2-a]indéno10- (1, 3-dimethyl-1 H-pyrazole-4-methylene) -5H, 10H-imidazo [1,2-a] indeno
[1 ,2-e]pyrazine-4-one, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imidazo[1, 2-e] pyrazine-4-one, 3- {10- [10-methyl-8- (3-methylureido) -4-oxo-4,5-dihydro-1 OH-imidazo acid
[1 ,2-a]indéno[1 ,2-e]pyrazinyl]aminocarbonyl}propionique,[1, 2-a] indeno [1, 2-e] pyrazinyl] aminocarbonyl} propionique,
(10'RS)-spiro[pyrrolidine-3, 10'-5'H, 10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine]-4'-one,(10'RS) -spiro [pyrrolidine-3, 10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-spiro[pipéridine-2,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine]- 4'-one,(10'RS) -spiro [piperidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] - 4'-one,
(10'RS)-spiro[pyrrolidine-2,10'-5'HJ0Η-imidazo[1 ,2-a]indéno[1,2-e]pyra- zine]-4'-one,(10'RS) -spiro [pyrrolidine-2,10'-5'HJ0Η-imidazo [1, 2-a] indeno [1,2-e] pyrazine] -4'-one,
(10'RS)-1-méthyl-spiro[pyrrolidine-2,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one, (+)-1 -méthyl-spiro[pyrrolidine-2,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine]-4'-one,(10'RS) -1-methyl-spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one , (+) - 1 -methyl-spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1, 2-a] indéno [1, 2-e] py- razine] -4'- one,
(-)-1 -méthyl-spiro[pyrrolidine-2J 0'-5'HJ 0'H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine]-4'-one, acide (1 O'RSM-oxo^-^'-oxo^'.δ'-dihydro-spirofpyrrolidine^.l 0'-10'H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique, spiro[pipéridine-4,10'-5Η,10'H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one, acide 4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pipéridine-4,10'-10'H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-1 -yl]}butyrique,(-) - 1 -methyl-spiro [pyrrolidine-2J 0'-5'HJ 0'H-imidazo [1, 2-a] indeno [1, 2-e] py- razine] -4'-one, acid (1 O'RSM-oxo ^ - ^ '- oxo ^'. Δ'-dihydro-spirofpyrrolidine ^ .l 0'-10'H-imi- dazo [1, 2-a] indéno [1, 2-e] pyrazine-1 -yl]} - butyric, spiro [piperidine-4,10'-5Η, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, acid 4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [piperidine-4,10'-10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -1 -yl]} butyric,
1 -phénylacétyl-spiro[pipéridine-4J 0'-5'HJ 0'H-imidazo[1 ,2-a]indéno[1 ,2-e] yrazine]-4'-one,1-phenylacetyl-spiro [piperidine-4J 0'-5'HJ 0'H-imidazo [1, 2-a] indeno [1, 2-e] yrazine] -4'-one,
1 -(méthylcarbamoyl)-spiro[pipéridine-4, 10'-5'H, 10'H-imidazo[1 ,2-a]indéno1 - (methylcarbamoyl) -spiro [piperidine-4, 10'-5'H, 10'H-imidazo [1, 2-a] indeno
[1 ,2-e]pyrazine]-4'-one,[1, 2-e] pyrazine] -4'-one,
1 -méthyl-spiro[pipéridine-4, 10'-5'H , 10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one, 1 -benzyl-spiro[pipéridine-4, 10'-5'H, 10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,1-methyl-spiro [piperidine-4, 10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, 1 -benzyl-spiro [piperidine-4, 10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
1-phénéthyl-spiro[pipéridine-4,10'-5'H,10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyra- zine]-4'-one, (10'RS)-1 -acétyl-spiro[pyrrolidine-2, 10'-δ'H, 10'H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,1-phenethyl-spiro [piperidine-4,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one, (10 ' RS) -1-acetyl-spiro [pyrrolidine-2, 10'-δ'H, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one,
(10'RS)-1-[(3-méthyluréido)acétyl]-spiro[pyrrolidine-2,10'-5'H,10'H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1 - [(3-methylureido) acetyl] -spiro [pyrrolidine-2,10'-5'H, 10'H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine] -4'-one,
(10'RS)-1-(phénylcarbamoyl)-spiro[pyrrolidine-2,10'-5Η,10'H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1- (phenylcarbamoyl) -spiro [pyrrolidine-2,10'-5Η, 10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine] -4'-one ,
(10'RS)-1-méthyl-8'-fluoro-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1,2-a] indéno[1 ,2-e]pyrazine]-4'-one,(10'RS) -1-methyl-8'-fluoro-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1,2-a] indeno [1, 2-e] pyrazine] -4'- one,
(10'RS)-1-éthyl-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one, (10'RS)-1-propyl-spiro[pyrrolidine-2,10'-5Η,10Η-imidazo [1 ,2-a]indéno[1 ,2-e] pyrazine]-4'-one,(10'RS) -1-ethyl-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one, (10 ' RS) -1-propyl-spiro [pyrrolidine-2,10'-5Η, 10Η-imidazo [1, 2-a] indéno [1, 2-e] pyrazine] -4'-one,
(10'RS)-4-oxo-4-{4'-oxo-4',5'-dihydro-spiro[pyrrolidine-2,10'-10Η-imidazo[1,2- a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique,(10'RS) -4-oxo-4- {4'-oxo-4 ', 5'-dihydro-spiro [pyrrolidine-2,10'-10Η-imidazo [1,2- a] indéno [1, 2 -e] pyrazine-1 -yl]} - butyric,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylate d'éthyle,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxamide,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxamide,
8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylate d'éthyle, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl azazine-2-carboxylate, acid 8- (3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
7-chloro-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxylate d'éthyle, acide 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide 10-(1 -pyrrolyle)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-7-chloro-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 4,5-dihydro- acid 4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 10- (1 -pyrrolyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid, 10-amino-4 acid, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-
2-carboxylique, acide 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zine-2-carboxylique, acide 7-chloro-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 8-amino-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 5-(2-carboxy-10-méthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno2-carboxylic, 10-hydroxyimino-4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 7-chloro-4 acid, 5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-amino-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 5- (2-carboxy-10-methyl-4,5-dihydro-4-oxo-10H-imidazo acid [1, 2 -a] indéno
[1 ,2-e]pyrazine-10-yl)valérique, acide 4,5-dihydro-4, 10-dioxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxy- lique, acide (E)-4,5-dihydro-4-oxo-10-(3-carboxybenzylidène)-imidazo[1 ,2-a]in- déno[1,2-e]pyrazine-2-carboxylique, acide 10-(3-carboxypropionylamino)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 10-(3-phényluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 10-[(1 -méthylimidazol-2-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthylène]-4,5-dihydro-4-oxo-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-2-yl)méthyl]-4,5-dihydro-4-oxo-1 OH-imidazo [1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 10-[(1-méthylimidazol-5-yl)méthyl]-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 4-[10-(2-carboxy-4,5-dihydro-4-oxo-imidazo[1 ,2-a]indéno[1 ,2-e]pyra- zinylidène)aminooxy]butyrique, 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-car- boxylate d'éthyle, acide 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2- carboxylique, acide 4-oxo-10-[1-(2-oxo-2,5-dihydropyrrolyl)]-4,5-dihydro-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yi)acé- tique,[1, 2-e] pyrazine-10-yl) valeric, 4,5-dihydro-4, 10-dioxo-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxy- lique, acid (E) -4,5-dihydro-4-oxo-10- (3-carboxybenzylidene) -imidazo [1, 2-a] ind deno [1,2-e] pyrazine-2-carboxylic acid 10- (3-carboxypropionylamino) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic acid 10- (3- phenylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-2-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-5-yl) methylene] -4,5-dihydro-4-oxo-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-2-yl) methyl] -4 , 5-dihydro-4-oxo-1 OH-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 10 - [(1-methylimidazol-5-yl) methyl] - 4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid 4- [10- (2-carboxy-4,5-dihydro -4-oxo-imidazo [1, 2-a] ind No. [1, 2-a] pyra- zinylidène) aminooxy] butyric 8-fluoro-4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 8-fluoro-4- acid oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic, 4-oxo-10- [1- (2-oxo-2,5 -dihydropyrrolyl)] - 4,5-dihydro-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic, acid (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yi) acetic,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)méthyl] acétamide,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] acetamide,
9-[(3-méthyluréido)méthyl]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxyiique,9 - [(3-methylureido) methyl] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, N-methyl- [4,5-dihydro-4- oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4,5-dihydro-4-oxo-10H-imidazo acid [1 , 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-2-carboxyique,
8-(3-méthyluréido)méthyl-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo- acid 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) carboxamide,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carboxamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)carbonyl] glycine,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) carbonyl] glycine,
N-benzyl-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno [1 ,2-e]pyrazine-2-carboxylique,N-benzyl- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, 8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic acid,
8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno [1 ,2- e]pyrazine-2-carboxylique, acide 8-(2-carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique, acide 9-[(3-méthyluréido)méthyl]-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]in- déno[1 ,2-e]pyrazine-2-carboxylique, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-N-méthylaminocarbonylméthyl-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indene no [1, 2-e] ethyl pyrazine-2-carboxylate, acid 9- N-benzylcarbamoyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2 e] pyrazine-2-carboxylic, 8- (2-carboxyethyl) acid -4.5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9 - [(3-methylureido) methyl] -4,5-dihydro-4 -oxo-1 OH-imidazo [1, 2-a] ind deno [1, 2-e] pyrazine-2-carboxylic, 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1 , 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 9-N-methylaminocarbonylmethyl-4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1 , 2-e] pyrazine-2-carboxylic, 9- (1 -carboxyethyl) -4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine -2-carboxylic,
9-(1 H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-phosphonique,9- (1 H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, acid 9- (1 H-tetrazole- 5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 9- (1 H- tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic,
4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique,4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic,
9-cyanométhyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 9-(4-phényl-1 H-imidazol-2-yl-méthyl)-4,5-dihydro-4-oxo-1 OH-imida- zo[1 ,2-a]indéno [1 ,2-e]pyrazine-2-carboxylique, acide 3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (E)-3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 9-benzènesulfonamidocarbonylméthyl-4-oxo-4,5-dihydro-1 OH-imidazo9-cyanomethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxymethyl-4-oxo-4,5-dihydro-10H-imidazo acid [1 , 2-a] indeno [1, 2-e] pyrazine-2-methylphosphonic acid 9- (4-phenyl-1 H-imidazol-2-yl-methyl) -4,5-dihydro-4-oxo -1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] py- razin-2-yl) -propionic, (E) -3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-yl) -acrylic acid, 4- acid oxo-9-phosphonomethyl-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 2- (4-carboxyphenyl) -4-oxo-4 acid , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 2- (3-carboxyphenyl) -4-oxo-4,5-dihydro-10H- imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, 2- (2-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a ] indeno [1, 2- e] pyrazine-9-acetic, 9-benzenesulfonamidocarbonylmethyl-4-oxo-4,5-dihydro-1 OH-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique, acide 9-méthylsulfonamido-carbonylméthyl-4-oxo-4,5-dihydro-1 OH-imidazo[1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 9-methylsulfonamido-carbonylmethyl-4-oxo-4,5-dihydro-1 OH-imidazo
[1 ,2-a]indéno[1 ,2-e]pyrazine-2-carboxylique, 1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,[1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione,
8-chloro-1 ,4-dihydro-5H-indeno[1 ,2-b]pyrazine-2,3-dione, acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5-yl)acéti- que,8-chloro-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-2,3-dione, acid (5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-5-yl) acetic,
5-amino-8-chloro-1 ,4-dihydro-5H-indéno[1,2-b]pyrazine-2,3-dione, 7-(3-phényluréido)-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-2,3-dione,5-amino-8-chloro-1, 4-dihydro-5H-indeno [1,2-b] pyrazine-2,3-dione, 7- (3-phenylureido) -1, 4-dihydro-5H-indeno [ 1, 2-b] pyrazine-2,3-dione,
(E)-5-carboxyméthylène-8-chloro-1 ,4-dihydro-indéno[1 ,2-b]pyrazine-2,3- dione, acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-5- yl)açétique, (+) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(E) -5-carboxymethylene-8-chloro-1,4-dihydro-indeno [1,2-b] pyrazine-2,3-dione, acid (8-chloro-5-methyl-2,3-dioxo- 1,4-dihydro-5H-indeno [1,2-b] pyrazine-5-yl) acetic, (+) acid (5-methyl-2,3-dioxo-1,4,4-dihydro-1H-indeno [1 , 2-b] pyrazine-5-yl) acetic,
(-) acide (5-méthyl-2,3-dioxo-1 ,4-dihydro-1 H-indéno[1 ,2-b]pyrazine-5-yl)acé- tique,(-) (5-methyl-2,3-dioxo-1, 4-dihydro-1 H-indeno [1, 2-b] pyrazine-5-yl) acetic acid,
(+) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine- 5-yl)acétique, (-) acide (8-chloro-5-méthyl-2,3-dioxo-1 ,4-dihydro-5H-indéno[1 ,2-b]pyrazine-(+) (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indeno [1, 2-b] pyrazine-5-yl) acetic acid, (-) acid (8-chloro-5-methyl-2,3-dioxo-1, 4-dihydro-5H-indéno [1, 2-b] pyrazine-
5-yl)acétique acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1(2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775), 1 ,4-dihydro-6-(1H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione (YM 900 et5-yl) acetic acid [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -quino-noxalinyl] methyl] phosphonic (ZK200775), 1,4-Dihydro-6- (1H-imidazol-1-yl) -7-nitro-2,3-quinoxalinedione (YM 900 and
YM90K), acide 3,4-dihydro-7-(1 H-imidazol-1 -yl)-6-nitro-2,3-dioxo-1 (2H)-quinoxaline- acétique (YM 872),YM90K), 3,4-dihydro-7- (1 H-imidazol-1 -yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic acid (YM 872),
1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX),1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide (NBQX),
1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),1, 4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),
1-(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4-di- hydro-5H-2,3-benzodiazépine (LY 300168),1- (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
(-)-3-Acétyl-1-(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H- 2,3-benzodiazépine (LY 300164), le composé Ro48-8587, acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1 H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490) acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le composé SH608(-) - 3-Acetyl-1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-2,3-benzodiazepine (LY 300164), the compound Ro48-8587, decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325), decahydro-6- [2- ( 1H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic (LY 293558), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl acid ] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490) (6,7-dichloro-1,2,2-dihydro-2-oxo-3-qinolinyl) phosphonic acid (S176252) SH608
leurs sels pharmaceutiquement acceptables et leurs énantiomères lorsqu'ils comportent un carbone asymétrique.their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
18 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est un antagoniste des récepteurs AMPA sélectif. 19 - Association selon la revendication 12 pour laquelle l'antagoniste des récepteurs AMPA est choisi parmi les composés suivants :18 - Association according to claim 12 for which the AMPA receptor antagonist is a selective AMPA receptor antagonist. 19 - Association according to claim 12 for which the AMPA receptor antagonist is chosen from the following compounds:
10-acétamido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,10-acetamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-hydroxyméthyl-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-amino-8-fluoro-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 10-(2-hydroxyéthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione, 9-phénylacétamido-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one, 8-éthoxycarbonylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(3-méthoxyphényl)uréido]-5HJ0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine- 4-one,10-amino-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-hydroxymethyl-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10-amino-8-fluoro-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 10- (2-hydroxyethyl ) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4,10-dione, 9-phenylacetamido-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 8-ethoxycarbonylamino-5H, 10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (3-methoxyphenyl) ureido] -5HJ0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine- 4 -one,
8-phénylacétamido-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénéthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-méthyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-benzyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-phénylpropionamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-benzamido-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(4-phénylbutyrylamino-5HJ0H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(5-phénylvalérylamino-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3,3-diméthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3-(2-méthoxyphényl)uréido]-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4- one, 8-(4-méthylpentanoyl)amino-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8-phenylacetamido-5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-methylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3 -benzylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-phenylpropionamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8-benzamido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- (4-phenylbutyrylamino -5HJ0H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one, 8- (5-phenylvalerylamino-5H, 10H-imidazo [1,2-a] indeno [1,2 e] pyrazine-4-one, 8- (3,3-dimethylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- ( 2-methoxyphenyl) ureido] -5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4- one, 8- (4-methylpentanoyl) amino-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one,
8-(3-méthylthiouréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-[3-(2-éthoxycarbonyléthyl)uréido]-5HJ0H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one, 8-[3-(3-fluorophényl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- (3-methylthioureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 8- [3- (2-ethoxycarbonylethyl) ureido] -5HJ0H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 8- [3- (3-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(2-fluorophényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(3-éthyluréido)-5H,10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one,8- [3- (2-fluorophenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (3-ethylureido) -5H, 10H -imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
10-amino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,10-amino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4 one,
10-hydroxyimino-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1,2-e] pyrazine-4-one, 8-(3-méthyluréido)-5H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4,10-dione,10-hydroxyimino-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 8- (3-methylureido) -5H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-4,10-dione,
8-[3-morpholino-uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- [3-morpholino-ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-thiouréido-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8-thiouréido-5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-propyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-propylureido) -5HJ 0H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-(3-isopropyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one, 8-(3-butyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one,8- (3-isopropylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one, 8- (3-butylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one,
8-[(2-thiazolin-2-yl)amino]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8 - [(2-thiazolin-2-yl) amino] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carbométhoxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]py- razine-4-one, 8-[3-(2-fluorobenzyl)uréido]-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-carbomethoxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 8- [3- (2-fluorobenzyl ) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-fluorobenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4- one,8- [3- (3-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4- one,
8-[3-(4-fluorobenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (4-fluorobenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(3-carboxyphényl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one,8- [3- (3-carboxyphenyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one,
8-[3-(4-carboxybenzyl)uréido]-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, 8-(1 ,3-diméthyluréido)-5HJ 0H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, 9-carboxamido-5H,10H-imidazo[1,2-a]indéno[1,2-e]pyrazine-4-one,8- [3- (4-carboxybenzyl) ureido] -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 8- (1, 3-dimethylureido) -5HJ OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, 9-carboxamido-5H, 10H-imidazo [1,2-a] indeno [1,2-e] pyrazine-4-one,
9-(3-méthyluréido)-5H,10H-imidazo[1,2-a]indéno[1 ,2-e]pyrazine-4-one,9- (3-methylureido) -5H, 10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-4-one,
9-(N-éthylcarboxamido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4-one, acide (4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)acé- tique,9- (N-ethylcarboxamido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid (4,5-dihydro-4-oxo-10H-imidazo [ 1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetic,
N-méthyl-2-(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl) acétamide,N-methyl-2- (4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) acetamide,
N-[(4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-9-yl)méthyl] acétamide, N-méthyl-[4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl] acétamide, acide 8-N-méthylcarboxamidométhyl-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-2-carboxylique, acide 8-carboxyméthyl-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,N - [(4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-9-yl) methyl] acetamide, N-methyl- [4,5 -dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl] acetamide, 8-N-methylcarboxamidomethyl-4,5-dihydro-4-oxo- 1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic, 8-carboxymethyl-4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a ] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(3-méthyluréido)méthyl-5H,10H-imidazo[1 ,2-a]indéno[1,2-e]pyrazine-4-one, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (3-methylureido) methyl-5H, 10H-imidazo [1, 2-a] indeno [1,2-e] pyrazine-4-one, 9-carboxymethyl-4,5-dihydro-4-oxo- acid 1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
N-benzyl-(4,5-dihydro-4-oxo-1 OH-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-8-yl) carboxamide, acide 8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno [1 ,2-e]pyrazine-2-carboxylique,N-benzyl- (4,5-dihydro-4-oxo-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-8-yl) carboxamide, acid 8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] pyrazine-2-carboxylic,
8-(N-éthylaminocarbonylméthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2- a]indéno[1 ,2-e]pyrazine-2-carboxylate d'éthyle, acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-phosphonique, acide 9-(1 -carboxyéthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-2-carboxylique,8- (N-ethylaminocarbonylmethyl) -4,5-dihydro-4-oxo-10H-imidazo [1, 2- a] indeno [1, 2-e] ethyl pyrazine-2-carboxylate, 9-carboxymethyl acid 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-phosphonic, 9- (1 -carboxyethyl) -4,5-dihydro-4 -oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic,
9-(1 H-tétrazole-5-yl-méthyl)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-4- one, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1 ,2-e]pyrazine-2-carboxylique, acide 9-(1 H-tétrazole-5-yl-méthyl)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indé- no[1,2-e]pyrazine-2-phosphonique, 4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2,9-diacétique, acide 9-carboxyméthyl-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-méthylphosphonique, acide 3-(9-carboxyméthyl-4-oxo-5, 10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razin-2-yl)-propionique, acide (£)-3-(9-carboxyméthyl-4-oxo-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-2-yl)-acrylique, acide 4-oxo-9-phosphonométhyl-5,10-dihydro-imidazo[1 ,2-a]indéno[1 ,2-e]py- razine-2-carboxylique, acide 2-(4-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(3-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, acide 2-(2-carboxyphényl)-4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-9-acétique, 10-( 1 -carboxy-1 -hydroxyméthyl)-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-4-one, acide 3-[10-(4-oxo-4,5-dihydro-10H-imidazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl) aminocarbonyl]propionique,9- (1 H-tetrazole-5-yl-methyl) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4- one, 9- (1 H-tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo acid [1, 2-a] indeno [1, 2-e] pyrazine-2- carboxylic acid 9- (1 H-tetrazole-5-yl-methyl) -4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno [1,2-e] pyrazine- 2-phosphonic, 4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2,9-diacetic, 9-carboxymethyl-4-oxo-4 acid , 5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazin-2-methylphosphonic acid 3- (9-carboxymethyl-4-oxo-5, 10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] pyrazin-2-yl) -propionic, acid (£) -3- (9-carboxymethyl-4-oxo-5,10-dihydro-imidazo [ 1, 2-a] indeno [1, 2- e] pyrazine-2-yl) -acrylic, 4-oxo-9-phosphonomethyl-5,10-dihydro-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-2-carboxylic acid 2- (4-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine -9-acetic, 2- (3-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-9-acetic, acid 2 - (2-carboxyphenyl) -4-oxo-4,5-dihydro-10H-imidazo [1, 2-a ] indeno [1, 2- e] pyrazine-9-acetic, 10- (1 -carboxy-1-hydroxymethyl) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1 , 2-e] pyrazine-4-one, 3- [10- (4-oxo-4,5-dihydro-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl) aminocarbonyl] acid propionic,
10-(carboxyméthylène)-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno [1 ,2- e]pyrazine-4-one,10- (carboxymethylene) -8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-4-one,
10-amino-10-méthyl-8-(3-méthyluréido)-5H,10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-10-yl]acétique, 10-amino-10-méthyl-8-(3-méthyluréido)-5H, 10H-imidazo[1 ,2-a]indéno[1 ,2-e] pyrazine-4-one, acide (+) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide (-) [8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1,2-a] indéno[1 ,2-e]pyrazine-10-yl]acétique, acide 3-{10-[10-méthyl-8-(3-méthyluréido)-4-oxo-4,5-dihydro-1 OH-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazinyl]aminocarbonyl}propionique, acide 8-(3-méthyluréido)-4,5-dihydro-4-oxo-10H-imidazo[1 ,2-a]indéno[1 ,2- e]pyrazine-2-carboxylique, acide (10'RS)-4-oxo-4-{4'-oxo-4',5,-dihydro-spiro[pyrrolidine-2,10'-10'H-imi- dazo[1 ,2-a]indéno[1 ,2-e]pyrazine-1 -yl]}-butyrique,10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, acid [8- (3-methylureido ) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, 10-amino-10-methyl-8- (3-methylureido) -5H, 10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-4-one, (+) acid [8- ( 3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, acid (-) [8- (3 -methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1,2-a] indeno [1, 2-e] pyrazine-10-yl] acetic, 3- {10- [10-methyl -8- (3-methylureido) -4-oxo-4,5-dihydro-1 OH-imidazo [1, 2-a] indeno [1, 2-e] pyrazinyl] aminocarbonyl} propionic acid 8- ( 3-methylureido) -4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2- e] pyrazine-2-carboxylic acid (10'RS) -4-oxo- 4- {4'-oxo-4 ', 5 , -dihydro-spiro [pyrrolidine-2,10'-10'H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine-1 -yl]} - butyric,
1 ,2,3,4-tétrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide
(NBQX), acide décahydro-6-[2-(1 H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558),(NBQX), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558),
1,4-dihydro-6-(1H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione (YM 900 et1,4-dihydro-6- (1H-imidazol-1-yl) -7-nitro-2,3-quinoxalinedione (YM 900 and
YM90K), acide [[3,4-dihydro-7-(4-morpholinyl)-2,3-dioxo-6-(trifluorométhyl)-1(2H)-qui- noxalinyl]méthyl]phosphonique (ZK200775), acide 3,4-dihydro-7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1(2H)-quinoxaline- acétique (YM 872),YM90K), acid [[3,4-dihydro-7- (4-morpholinyl) -2,3-dioxo-6- (trifluoromethyl) -1 (2H) -qui- noxalinyl] methyl] phosphonic acid (ZK200775), acid 3 , 4-dihydro-7- (1H-imidazol-1-yl) -6-nitro-2,3-dioxo-1 (2H) -quinoxaline- acetic (YM 872),
1 ,4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),1, 4-dihydro-6,7-dinitro-2,3-quinoxalinedione (DNQX),
1-(4-aminophényl)-3-méthylcarbamoyl-4-méthyl-7,8-méthylènedioxy-3,4- di- hydro-5H-2,3-benzodiazépine (LY 300168),1- (4-aminophenyl) -3-methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4-di-hydro-5H-2,3-benzodiazepine (LY 300168),
(-)-3-Acétyl-1-(4-aminophényl)-4-méthyl-7,8-méthylènedioxy-4,5-dihydro-3H-(-) - 3-Acetyl-1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-
2,3-benzodiazépine (LY 300164), acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 326325), acide décahydro-6-[2-(1 H-tétrazol-5-yl)éthyl]-(3S,4aR,6R,8aR)-3-isoquino- léinecarboxylique (LY 293558), acide décahydro-6-[2-(1H-tétrazol-5-yl)ethyl]-(3R,4aS,6S,8aS)-3-isoquino- léinecarboxylique (LY 215490), acide (6,7-dichloro-1 ,2-dihydro-2-oxo-3-qinolinyl)phosphonique (S176252), le composé Ro48-8587, le composé SH608 leurs sels pharmaceutiquement acceptables et leurs énantiomères lorsqu'ils contiennent un carbone asymétrique.2,3-benzodiazepine (LY 300164), decahydro-6- [2- (1H-tetrazol-5-yl) ethyl] - (3R, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 326325), decahydro-6- [2- (1 H-tetrazol-5-yl) ethyl] - (3S, 4aR, 6R, 8aR) -3-isoquino-leinecarboxylic acid (LY 293558), decahydro-6- [2- ( 1H-tetrazol-5-yl) ethyl] - (3R, 4aS, 6S, 8aS) -3-isoquino-leinecarboxylic (LY 215490), acid (6,7-dichloro-1, 2-dihydro-2-oxo-3 -qinolinyl) phosphonic (S176252), the compound Ro48-8587, the compound SH608 their pharmaceutically acceptable salts and their enantiomers when they contain an asymmetric carbon.
20 - Association du riluzole ou un de ses sels pharmaceutiquement acceptables et de l'acide 9-carboxyméthyl-4,5-dihydro-4-oxo-10H- imidazo[1 ,2-a]indéno[1 ,2-e]pyrazine-2-phosphonique ou un de ses sels pharmaceutiquement acceptables.20 - Association of riluzole or one of its pharmaceutically acceptable salts and of 9-carboxymethyl-4,5-dihydro-4-oxo-10H-imidazo [1, 2-a] indeno [1, 2-e] pyrazine acid -2-phosphonic acid or one of its pharmaceutically acceptable salts.
21 - Utilisation du riluzole ou un de ses sels pharmaceutiquement acceptablés pour la préparation d'une association selon l'une des revendicartions 12 à 20.21 - Use of riluzole or one of its pharmaceutically acceptable salts for the preparation of an association according to one of claims 12 to 20.
22 - Composition pharmaceutique constituée d'une association du riluzole ou un de ses sels pharmaceutiquement acceptables et d'un ou plusieurs antagonistes des récepteurs AMPA à l'exception du CNQX et du GYKI52466, à l'état pur ou en présence de tout diluant ou adjuvant compatible et pharmaceutiquement acceptable. 22 - Pharmaceutical composition consisting of a combination of riluzole or one of its pharmaceutically acceptable salts and one or more antagonists of AMPA receptors with the exception of CNQX and GYKI52466, in the pure state or in the presence of any diluent or compatible and pharmaceutically acceptable adjuvant.
EP00910920A 1999-03-12 2000-03-10 Amyotropic lateral sclerosis treatment with a combination of riluzole and an ampa receptor antagonist Withdrawn EP1161238A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
FR9903100 1999-03-12
FR9903100A FR2790670A1 (en) 1999-03-12 1999-03-12 Treatment or prevention of amyotrophic lateral sclerosis, using synergistic combination of riluzole and AMPA receptor antagonist, e.g. 5H,10H-imidazo (1,2-a) indeno (1,2-e) pyrazin-4-one derivative
US12931899P 1999-04-14 1999-04-14
US129318P 1999-04-14
PCT/FR2000/000590 WO2000054772A1 (en) 1999-03-12 2000-03-10 Amyotropic lateral sclerosis treatment with a combination of riluzole and an ampa receptor antagonist

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MXPA04009496A (en) 2002-03-29 2005-01-25 Yamanouchi Pharma Co Ltd Remedy for glioblastoma.
US7045527B2 (en) 2002-09-24 2006-05-16 Amgen Inc. Piperidine derivatives
CA2632635C (en) * 2005-12-08 2014-04-29 Hybrigenics Sa Novel inhibitors of cysteine proteases, the pharmaceutical compositions thereof and their therapeutic applications
EP1798232A1 (en) * 2005-12-08 2007-06-20 Hybrigenics S.A. Inhibitors of cysteine proteases, the pharmaceutical compositions thereof and their therapeutic applications
WO2010113225A1 (en) * 2009-03-30 2010-10-07 Yutoku Pharmaceutical Industries Co., Ltd. Riluzole-containing transdermal patch

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FR2722789B1 (en) * 1994-07-20 1996-08-23 Rhone Poulenc Rorer Sa IMIDAZO (1,2-A) INDENO (1,2-E) PYRAZINE-2-CARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM
US5780489A (en) * 1996-08-21 1998-07-14 Brooks; Benjamin Rix Method for treating amyotrophic lateral sclerosis
EP1829539A3 (en) * 1996-11-05 2008-02-20 HEADEXPLORER ApS A method for treating tension-type headache
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