FR2945530A1 - New triamino-pyrimidine derivatives are cell division cycle 25 phosphatase inhibitors useful for treating or preventing e.g. cancer, neurodegenerative diseases, parasitic diseases, viral infections, autoimmune diseases and melanomas - Google Patents

Abstract

Triamino-pyrimidine derivatives (I) and their salts, racemic forms and/or enantiomers are new. Triamino-pyrimidine derivatives of formula (I) and their salts, racemic forms and/or enantiomers are new. R 1>aryl, aralkyl, heteroaryl, heteroarylalkyl (all optionally substituted by one or more groups of T), pyrimidine group of formula (a) or -COR 8>; T : alkyl, haloalkyl, nitro, halo, alkoxy, CN, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino or dialkylamino; R 2>H, 1-3C alkyl, or heteroaryl (optionally substituted by T); W 1>-NR 6>-, -CR 6>R 7>-, O or S; R 6>, R 7>H or alkyl; n, q : 0-6, where n and q are not simultaneously 0; R 3>H or alkyl; either R4a, R4b, R5a, R5b : H, alkyl, aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl; or NR4aR5a, NR4bR5b : heterocycloalkyl; and R 8>aryl, aralkyl, heteroaryl, or heteroarylalkyl (all optionally substituted by one or more groups of T), 1-15C alkyl, heteroarylthioalkyl, or 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene moiety. An independent claim is included for the preparation of (I). [Image] [Image] ACTIVITY : Cytostatic; Neuroprotective; Antiparasitic; Virucide; Endocrine-Gen.; Immunosuppressive; Antiinflammatory; Antiallergic. MECHANISM OF ACTION : Cell division cycle 25 (CDC25) phosphatase inhibitor. The ability of (I) to inhibit CDC25 phosphatase was tested in vitro. The result showed that N'-(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)-N-methyl-N-[2-(pyrimidin-2-ylamino)ethyl]ethane-1,2-diamine hydrochloride exhibited an IC 50value of = 10 mu M.

Description

The present invention relates to novel triamino-pyrimidine derivatives. These products have a Cdc25 phosphatase inhibitory activity. The invention also relates to a process for synthesizing these compounds as well as therapeutic compositions containing these products and their use as a medicament. The control of the transition between the different phases of the cell cycle during mitosis or meiosis is provided by a set of proteins whose enzymatic activities are associated with different states of phosphorylation. These states are controlled by two major classes of enzymes: kinases and phosphatases. The synchronization of the different phases of the cell cycle thus allows the reorganization of cellular architecture at each cycle throughout the living world (microorganisms, yeasts, vertebrates, plants). Among kinases, cyclin-dependent kinases (CDKs) play a major role in this control of the cell cycle. The enzymatic activity of these different CDKs is controlled by two other families of enzymes that work in opposition (Jessus and Ozon, Prog Gell Cycle Res (1995), 1, 215-228). The first group includes kinases such as Weel and Miki that deactivate CDKs by phosphorylating certain amino acids (Den Haese et al., Mol Biol Gell (1995), 6, 371-385). The second group includes phosphatases such as Cdc25 which activate CDKs by dephosphorylating tyrosine and threonine residues of CDKs (Gould et al., Science (1990), 250, 1573-1576). Phosphatases are classified into 3 groups: serine / threonine phosphatases (PPases), tyrosine phosphatases (PTPases) and dual specificity phosphatases (DSPases). These phosphatases play an important role in the regulation of many cellular functions. For human Cdc25 phosphatases, 3 genes (Cdc25-A, Cdc25-B and Cdc25-C) encode Cdc25 proteins. In addition, variants derived from alternative splicing of the Cdc25B gene have been identified: it is Cdc25B1, Cdc25B2 and Cdc25B3 (Baldin et al., Oncogene (1997), 14, 2485-2495).

The role of Cdc25 phosphatases in oncogenesis is now better known and the mechanisms of action of these phosphatases are illustrated in particular in the following references: Galaktionov et al., Science (1995), 269, 1575-1577; Galaktionov et al., Nature (1996), 382, 511-517; and Mailand et al., Science (2000), 288, 1425-1429.

The overexpression of the different forms of Cdc25 is now reported in many series of human tumors, for example: - Breast cancer: cf. Cangi et al., Abstract 2984. AACR meeting San Francisco, 2000); - Lymphomas: cf. Hernandez et al., Int. J. Cancer (2000), 89, 148-152 and Hernandez et al., Cancer Res. (1998), 58, 1762-1767; - Cancers of the neck and head: cf Gasparotto et al., Cancer Res. (1997) 57. 2366-2368; - Pancreatic cancers: cf. Junchao Guo et al., Oncogene (2004), 23, 71-81. In addition, the group of E. Sausville reports an inverse correlation between the level of expression of Cdc25-B in a panel of 60 lines and their sensitivities to CDK inhibitors, suggesting that the presence of Cdc25 may bring resistance to certain agents. antitumor and more particularly to CDK inhibitors (Hose et al., Proceedings of AACR Abstract 3571, San Francisco, 2000). Among other targets, we are now looking for compounds capable of inhibiting Cdc25 phosphatases for use in particular as anti-cancer agents. Cdc25 phosphatases also play a role in neurodegenerative diseases (see Zhou et al., Cell Mol Lifé Sci (1999), 56 (9-10), 788-806, Ding et al., Am. (2000), 157 (6), 1983-90, Vincent et al., Neuroscience (2001), 105 (3), 639-50) so that one can also consider using compounds having an activity. inhibition of these phosphatases to treat these diseases. Another problem addressed by the invention is the search for drugs intended to prevent or treat rejection of organ transplants or to treat autoimmune diseases. In these disorders and / or diseases, inappropriate activation of lymphocytes and monocytes / macrophages is involved. However, immunosuppressive drugs known to date have side effects that could be reduced or modified by products specifically targeting signaling pathways in hematopoietic cells that initiate and maintain inflammation. The triamino-pyrimidine derivatives as defined below are new Cdc25 phosphatase inhibitors. They are likely to be used as medicaments, particularly in the treatment and / or prevention of the following diseases or disorders: • inhibition of tumor proliferation, alone or in combination with other treatments; • cancers; • inhibition of normal cell proliferation, alone or in combination with other treatments; • neurodegenerative diseases; • prevention of spontaneous alopecia; • the prevention of alopecia induced by exogenous products; • prevention of radiation-induced alopecia; • the prevention of spontaneous or induced apoptosis of normal cells; • the prevention of meiosis and / or fertilization; • prevention of oocyte maturation; All diseases and / or disorders corresponding to reported uses for inhibitors of CDKs, and in particular non-tumor proliferative diseases (for example: angiogenesis, psoriasis or restenosis), proliferative tumoral diseases, parasitic diseases (proliferation of protozoa ), viral infections, neurodegenerative diseases, myopathies; and / or • all diseases and / or disorders corresponding to clinical applications of vitamin K and its derivatives.

Moreover, the compounds of the present invention are also, because of their Cdc25 phosphatase inhibiting properties, capable of being used to inhibit or prevent the proliferation of microorganisms, especially yeasts. One of the advantages of these compounds is their low toxicity on healthy cells. Thus, the subject of the present invention is a compound of general formula (I) R 4b -R 5b in racemic or enantiomeric form or any combination thereof, in which: R 1 represents one of the following aryl radicals optionally substituted with one or several identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl. amino. alkylamino, dialkylamino, aralkyl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, optionally substituted heteroaryl by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl. aminosulfonyl, amino. alkylamino, dialkylamino, heteroarylalkyl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, a radical of formula: R4b R5b N N R4a N N R5a a radical of formula ùCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo.

alkoxy, cyano. alkoxycarbonyl, dialkylaminosulfonyl, aralkyl. aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino; W represents NR6, CR6R7, oxygen or sulfur; R6 and R7 independently represent a hydrogen atom or an alkyl radical: n or q are integers between 0 and 6 inclusive, provided that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a, R4b, R5a and R5b independently represent a hydrogen atom, an alkyl, aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl radical; or R4a and R5a and / or R4b and R5b together with the nitrogen atom to which they are attached form a heterocycloalkyl radical; R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, aralkyl optionally substituted by one or more identical groups or

various selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl,

dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino. heteroarylalkyl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, alkyl having from 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof, it being understood that R2 represents a heteroaryl radical only if RI also represents this same heteroaryl radical. By alkyl, when not more precise is meant a linear or branched alkyl radical having 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, such as methyl. ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, or hexyl. For the purposes of the present invention, alkylamino or dialkylamino is understood to mean an amino radical substituted with one or two alkyl radicals as defined above. By aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl, is meant a sulfonyl radical (-SO2-) substituted by an amino, alkylamino or dialkylamino radical as defined above. By haloalkyl is meant an alkyl radical as defined above substituted with one or more identical or different halogen atoms such as, for example, trifluoromethyl or pentafluoroethyl. The alkyl radical of the alkoxy and alkoxycarbonyl groups is as previously defined.

Heterocycloalkyl within the meaning of the present invention is understood to mean a ring having from 3 to 6 members and comprising one or more identical or different heteroatoms chosen from O. N and S, for example an azeridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl radical. .

By aryl is meant an unsaturated carbocyclic system comprising at least one aromatic ring, and preferably a radical selected from phenyl, naphthyl and fluorenyl. By arylalkyl is meant an alkyl radical as defined above substituted with an aryl radical as defined above, such as, for example, the benzyl radical or the phenethyl radical.

Heteroaryl within the meaning of the present invention means an aromatic unsaturated ring comprising one or more identical or different heteroatoms chosen from N, O and S such as furyl, thienyl, purinyl, benzothiazolyl, isoxazolyl, benzothiadiazolyl, pyridinyl, oxazolyl, pyrazolyl, pyrimidinyl or quinoxalyl and preferably the heteroaryl radical represents a pyridinyl, pyrimidinyl, purinyl, or benzothiazolyl radical.

By heteroarylalkyl is meant an alkyl radical substituted with a heteroaryl as defined above, such as for example the furylmethyl radical. For the purposes of the present invention, heteroarylthioalkyl is understood to mean a heteroaryl-S-alkyl-radical in which the heteroaryl and alkyl radicals are as defined previously, for example the pyrimidinylthiomethyl radical.

By salt of a compound is meant the addition salts of said compound with an organic or inorganic acid and in particular the pharmaceutically acceptable salts of said compound. By pharmaceutically acceptable salt is meant in particular inorganic acid addition salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, diphosphate and nitrate or organic acids such as acetate, maleate, fumarate, tartrate, succinate, citrate. lactate, methanesulfonate, p-toluenesulfonate, pamoate and stearate; preferably, the hydrochloride. For other examples of pharmaceutically acceptable salts, reference may be made to "Salt selection for basic drugs", Int. J. Pharm. (1986), 33, 201-217.

In certain cases, the compounds according to the present invention may comprise asymmetric carbon atoms. Therefore, the compounds of the present invention have two possible enantiomeric forms, i.e. the "R" and "S" configurations. The present invention includes both enantiomeric forms and any combinations of these forms, including racemic "RS" mixtures. For the sake of simplicity, when no specific configuration is indicated in the structural formulas, it should be understood that the two enantiomeric forms and their mixtures are represented. Preferably, the subject of the invention is a compound as defined above in which RI does not represent a -COR8 radical.

Also preferably, the subject of the invention is a compound as defined above in which R 1 represents a -COR 8 radical. Preferably, the subject of the invention is a compound as defined above in which R4a and R5a, and R4b and R5b, together with the nitrogen atom to which they are attached, form a heterocycloalkyl radical.

Preferably, the subject of the invention is a compound as defined above in which W represents -NR6-. Preferentially also. the subject of the invention is a compound as defined above in which W represents -CR6R7-. More preferably, the subject of the invention is a compound as defined above in which R 1 represents one of the following aryl radicals optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro and halo. , alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, heteroaryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, a radical of the formula: R4b, R5b NN R4a NN R5a a radical of the formula; R2 represents a hydrogen atom, a linear or branched alkyl radical containing from 1 to 3 carbon atoms or a heteroaryl radical optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo,

alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino; W represents NR 6, R 6 R 7 R 6 and R 7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a, R4b, R5a and R5b independently represent a hydrogen atom, an alkyl radical, an aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl radical; or R4a and R5a and / or R4b and R5b form together with the nitrogen atom to which they are attached a heterocycloalkyl radical R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, 9 a radical of formula or a pharmaceutically acceptable salt of this compound. Even more preferably, the subject of the invention is a compound as defined above in which: R1 represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano. alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl. amino, alkylamino. dialkylamino, heteroaryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy. cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulphonyl, amino, alkylamino, dialkylamino, a radical of the formula R4b ,, ,, R5b N a radical of the formula ûCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6 0, R 6 R 7 R 6 and R 7 independently represent a hydrogen atom or an alkyl radical; N or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and R4b and R5b together with the nitrogen atom to which they are attached form a heterocycloalkyl radical; R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof. Even more preferably, the subject of the invention is a compound as defined above in which R1 represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro , halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, heteroaryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulphonyl, amino, alkylamino, dialkylamino, a radical of formula: R4b, R5b NN R4a-n N R5a a radical of formula ùCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6 0, CR 6 R 7 0; R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive provided that n and q are not 0 at the same time R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and Rob and R5b, together with the nitrogen atom to which they are attached, form a heterocycloalkyl radical; R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino . alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof. Very preferably, the subject of the invention is a compound as defined above in which R 1 represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, heteroaryl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, a radical of formula: R4b. R5b N N R4a-N R5a a radical of formula ûCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6 0, R 6 R 7 R 6 and R 7 independently represent a hydrogen atom or an alkyl radical; n or q are integers from 0 to 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and R4b and R5b together with the nitrogen atom to which they are attached form a heterocycloalkyl radical; R8 represents one of the following aryl radicals substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl a radical of formula: or a pharmaceutically acceptable salt thereof. Very preferably, the subject of the invention is a compound as defined above in which: R 1 represents one of the following aryl radicals optionally substituted with one or more identical or different groups chosen from alkyl, nitro, heteroaryl optionally substituted by one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, aralkyl, a radical of formula: R4b ~ R5b NN R4a '' NN R5a a radical of formula: ## STR2 ## R2 represents a hydrogen atom, or a heteroaryl radical; W represents NR 6 0, CR 6 R 70; R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom; R4a and RSa, and R4b and R5b, together with the nitrogen atom to which they are attached, form a heterocycloalkyl radical R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl , nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof. Even more preferably, the subject of the invention is a compound as defined above in which one or more of the following proposals is satisfied: the term heterocycloalkyl denotes a pyrrolidine or a piperidine, the term aryl represents the phenyl radical, aralkyl is benzyl, heteroaryl is pyridinyl, pyrimidinyl, purinyl, or benzothiazolyl, and heteroarylthioalkyl is pyrimidinylthiomethyl, or a pharmaceutically acceptable salt thereof. In particular, the subject of the invention is a compound of general formula (I) chosen from one of the following compounds: N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl- N- [2- (pyrimidin-2-ylamino) ethyl] ethane-12-diamine; N- {2 - [(2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} -N-methyl-N ', N'-dipyridin-2-ylethane-1,2-diamine N- (2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) -N-methyl-N- [2- (pyridin-2-ylamino) ethyl] ethane-1,2-diamine; N '- (4-tert-butylphenyl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2-diamine; N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2 - [(4-nitrophenyl) amino] ethyl} ethane-1,2-diamine; N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- [2- (7H-purin-6-ylamino) ethyl] ethane-1,2-diamine; N '- (2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) -N-methyl-N- (2 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} ethyl) ethane-1,2 -diamine; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -2- (pyrimidin-2-ylsulfanyl) acetamide; N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -2- (pyrimidin-2-ylsulfanyl) acetamide; N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2 - [(5-nitropyrimidin-2-yl) amino] ethyl} ethane-1,2-diamine N 1- (6-Chloropyrimidin-4-yl) -N- {2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2-diamine; N- {2- [{2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -4-nitrobenzamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -3- (trifluoromethyl) benzamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -3,5-bis (trifluoromethyl) benzamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} hexadecanamide: N- {2 - [{2 - [(2.6 1-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl] (methyl) amino] ethyl) -4-octylbenzamide N-2 - [{2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl (methyl) amino] ethyl) -3-fluoro-4-nitrobenzamide: N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl -4-nitro-3 - (trifluoromethyl) benzamide; N- {2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -4-fluoro-3-nitrobenzamide: Methyl4 - ({2- [ {2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) aminolethyl} carbamoyl) -2-nitrobenzoate; 4-butoxy-N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethylbenzamide; N1-2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl] -5,5,8,8-tetramethyl-5,6,7,8- tetrahydronaphthalene-2-carboxamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -2,3,4,5,6-pentafluorobenzamide: 4- ( dipropylsulfamoyl) -N- {2- [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} benzamide; 4-cyano-N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} benzamide; N-1,3-benzothiazol-2-yl-N-2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2-diamine N, N'-bis (2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) pentane-1,5-diamine; N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2 -diamine; N '- (9-Benzyl-9H-purin-6-yl) -N-2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl] -N-methylethane-1,2-tetraamine diamine:

N '- (7-Benzyl-7H-purin-6-yl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2 -Diamine: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2 - [(9-methyl-9H-purin-6-yl) amino] ethyl} ethane -1,2-diamine; N6- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -7H-purine-2,6-diamine; or a pharmaceutically acceptable salt thereof. Depending on the nature of the variables R1, R2, W, R3, R4a, R4b, R5a, R5b, n and q, the compounds of general formula (I) according to the invention may correspond to the compounds of formulas (Ia), (Ib) (Ie) or (Id) and they can be prepared according to the methods described below. The reagents used, the synthesis of which is not described below, are either commercially available or synthesized from them according to techniques known to those skilled in the art.

The synthesis passes through a key intermediate of general formula (IV),

R4a R5b 1 1 NNN R5a z "which can be synthesized in two ways depending on the nature of the groups R4a, R5a, R4b, R5b: a) When the groups -NR4aR5a and -NR4bR5b are different, the amines HNR4aR5a and HNR4bR5b react successively to obtain the compound of formula R4b Nom / 20

19, in which Z, Z 'and Z "represent a halogen atom and preferably a chlorine atom R5b R4a R5b i II R5bR4bNH z ~ NIN R4b R5aR4aNH R5aNN NR4b N z Al scheme Thus, the di-aminopyrimidine derivatives of general formula (IV) may be prepared in two synthetic steps by reacting, for example, the compound (II) with the amine compound of general formula R5bR4bNH in which R4b and R5b have been defined. previously, at a temperature between -5 ° C and 5 ° C (preferably 0 ° C), in an inert solvent such as for example tetrahydrofuran. The compound (III) thus obtained reacts with the amine compound of the general formula R5aR4aNH in which R4a and R5a have previously been defined, at a temperature of between 50 ° C. and 70 ° C. (preferably 65 ° C.) in a polar solvent and inert such as tetrahydrofuran. b) When the group -NR4aR5a is identical to the group -NR4bR5b, the same amine HNR4aR5a or HNR4bR5b makes it possible to obtain the compound of general formula (IV)

according to the following reaction scheme A2 wherein z, z 'and z "represent a halogen atom and preferably a chlorine atom R4a R5b z-N -z I I N) R5aR4aNH R5a, NNNR4b N z" or

R5bR4bNH z "

(IV) Scheme A2 Thus, the di-aminopyrimidine derivatives of general formula (IV) can be prepared according to the method described by Bundy et al. In Journal of Medicinal Chemistry, 1995, 35, 4161-4163 by reacting, for example, the compound ( II) with the amine compound of the general formula R5aR4aNH or R5bR4bNH wherein R4a, R5a, R4b and R5b have been defined as above, at a temperature between -5 ° C and 5 ° C (preferably 0 ° C) in an inert solvent such as, for example, tetrahydrofuran In the particular case where R4a, R5a, R4b and R5b all represent a methyl radical and in the particular case where the groups -NR4aR5a and NR4bR5b represent an ethylamino group, the conditions of the compounds of the formula (IV) are as described by Atri et al in Journal of Medicinal Chemistry, 1984. 27, 1621-1629. The reaction is carried out at a temperature of between 30 ° C. and 50 ° C. (preferably 40 ° C) in a polar solvent and inert such as for example ethanol. Preparation of intermediates of general formula (I int) in which R1 represents a hydrogen: R4a R5b R3Nz "N R5a NN R4a R3 wq NH R2 (1 int) R5a R4b R5b R4b N .q NH R2 NH n W (V) scheme As described in Scheme B above, the compounds of the general formula (I int) in which R 2, R 3, R 4a, R 4b, R 5a, R 5b, W, n and q are as previously defined and R 1 represents a hydrogen atom. hydrogen can be obtained, for example, by heating to a temperature of between 150 ° C and 250 ° C (preferably 190 ° C) or by microwave treatment, the compound of formula (IV) wherein z "represents a halogen atom and preferably a chlorine atom, with a large excess of the diamine compound (V).

Preparation of the compound of general formula (I) in which RI represents an aryl, aralkyl, heteroaryl or heteroarylalkyl radical (compound of general formula (Ia)): R5b R4b Nn R5a 1 N-NN R4a R3 R1 R5a R5b R4b R4b Embedded image As described in Scheme C above, the compounds of the general formula (Ia) in which R 2. R3, R4a, R4b. R5a, R5b, W, n, and q are as defined above, and R1 represents an aryl, aralkyl, heteroaryl, heteroarylalkyl radical can be obtained for example, by reacting the compound of general formula (VI) in which Z 'represents a halogen atom and preferably a chlorine atom or a bromine atom, on the compound of formula (I int) in the presence of a mineral acid trap such as a tertiary amine compound such as triethylamine at a temperature of between 20 ° C and 80 ° C in a solvent such as, for example, dichloromethane, tetrahydrofuran or ethanol according to methods known to those skilled in the art. These same compounds of general formula (Ia) can also be prepared under conditions similar to those of the Ullmann-Goldberg reaction, by reacting a halogenated compound of general formula (VI) in which Z 'represents a halogen atom. and preferably an iodine atom on the compound (I int) in the presence of a copper catalyst, preferably copper iodide and an organic base. preferably sodium acetate. The reaction is carried out at a temperature between 60 ° C and 80 ° C in a polar solvent such as for example DMF or DMSO, as described by Okano et al. In Organic Letters, 2003, 5, 26, 4987-4990 . In the particular case where R2 and R1 respectively represent a hydrogen atom and a pyridyl radical, the conditions for the preparation of the derivatives of formula (Ia) are as described according to the method of Buchwald by Usui et al. In Bioorganic & Medicinal Chemistry Letters , 2006, 16, 3249-3254. The reaction is carried out in the presence of a palladium catalyst. preferably tris (dibenzylideneacetone) dipalladium (0), a ligand, preferably 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl and an organic base such as sodium tertbutylate. The reaction is carried out at a temperature of between 60 ° C. and 80 ° C. (preferably at 70 ° C.) in an apolar and inert solvent such as, for example, toluene.

Preparation of the Compound of General Formula (I) wherein R1 is -COR8 (Compound of General Formula (Ib)): NNN R4a R3 (I int) (Ib) Scheme D As described in Scheme D above, compounds of formula wherein R 2, R 3, R 4a, R 4b, R 5a, R 5b, W, n and q are as previously defined and R 1 is -COR 8 may be obtained, for example, by condensing the acyl halide compound of the formula (VII) wherein z "represents a halogen atom and preferably a chlorine atom, on the compound of formula (I int) in the presence of a mineral acid trap such as a tertiary amine compound such as triethylamine or diisopropylethylamine at a temperature of between 10 ° C. and 30 ° C. (preferably 20 ° C.) in an inert solvent such as, for example, dichloromethane or ethyl ether, according to methods known to those skilled in the art. these same compounds of formula (Ib) can be prepared under conditions similar to the peptide couplings, by reacting the carboxylic acid of general formula (VIII) with the compound (I int) at a temperature of between 10 ° C. and 30 ° C. (preferably 20 ° C) in an inert solvent such as, for example, dichloromethane or 1,2-dichloromethane, as described in Scheme E below. R5b R4b N R8 R5b R4b N 'N1 R5a I (VII) R4a R4a R5a N5 R4a R8a R8a R5a R5a R5a R5a R5a R5b R5a R3 ## STR5 ## wherein R 2 and R 1 are both identical (and preferably a pyridyl radical, (Ie): R5b R4b ## STR1 ## R5a R4a R3 NH (VI Het) NNn W ~, Het R2 1 N R4a R3 Het (tint) (Ic) Scheme F Described in Scheme F in which Het represents a heteroaryl radical, the conditions for the preparation of the derivatives of formula (Ie) from the compounds of general formula (I int) in which R2 is a hydrogen, are as described by Usui et al. in Bioorganic & Medicinal Chemistry Letters, 2006, 16, 32-19-3254 according to the Buchwald method. The reaction is carried out in the presence of a palladium catalyst, preferably tris (dibenzylideneacetone) dipalladium (0), a ligand, preferably 2,2'-bis (diphenylphosphino) -1, 1'-binaphthyl and an organic base such as sodium tert-butylate. The reaction is carried out at a temperature between 60 ° C. and 80 ° C. (preferably at 70 ° C.) in an apolar and inert solvent such as, for example, toluene. Preparation of the compound of general formula (I) in which RI represents a diaminopyrimidine radical (compound of general formula (Id)): R2 = H R5a R4a R5b R3N N R4bNH nWnNH R2 R5a scheme G As described in scheme G above, the compounds of general formula (Id) in which R 2, R 3, R 4a, R 4b, R 5a, R 5b, W, n and q are as defined above and R 1 represents a diaminopyrimidine radical, can be obtained, for example, by heating at a temperature between 150 ° C and 250 ° C (preferably 190 ° C) or by microwave treatment, the compound of formula (IV) wherein z "represents a halogen atom and preferably a chlorine atom, with a half equivalent of the diamine compound of general formula (IX).

Thus the invention also relates to a process for preparing a compound of general formula (I) as defined above, or from the compound of general formula (I int) R 5b R 4b N R 5a (I int) in which R2, R3, R4a, R5a, R4b, R5b, W, n and q are as defined above and with which: a) a compound of the general formula R1-Z '(VI) in which Z is reacted; represents a halogen atom and RI represents an aryl, aralkyl, heteroaryl or heteroarylalkyl radical to give the compound of general formula (Ia), R5b R4b N "\\ R5a q N, R1 NNN W R4a R3 1 R2 compound of formula wherein R1 is aryl, aralkyl, heteroaryl or heteroarylalkyl, or b) a compound of the general formula R8CO2- (VII) or R8COOH (VIII) wherein R8 is as defined above and Z " represents a halogen atom to yield the compound of general formula (Ib) R5a n W R5b R4b 'N' q N R8 R2 compound of general formula (I) in which R1 is --OR8; or from the compound of general formula (I int) in which R3, R4a, R5a. 4b. 5b. W, n and q are as defined above and R2 is a hydrogen atom, with which a compound of the general formula Het-Z '(VI Het) in which Het and Z' respectively represent a heteroan and a halogen atom, to give the compound of general formula (Ic), R5b R4b 'N' R5a NIIII \\ NWN NN R4a R3 q N, Het Het compound of general formula (I) wherein R2 and R1 both represent an identical heteroaryl radical - either from the intermediate of the general formula (IV) R5a R5b ## STR2 ## wherein R4a, R5a, R4b, R5b are as defined above and Z represents a halogen atom, with which a compound of general formula (VII) R 2 QH 1 is reacted in which W, R 2, R 3, n and q are as defined above to yield the compound of general formula (Id) R 4a 7R5a -N q NNN / -R4b R2 R ~ R5a compound of general formula (I) wherein R1 represents a diaminopyrimid radical ine. The compounds of general formula (I) according to the present invention possess interesting pharmacological properties: they have a Cdc25 phosphatase inhibitory activity. They can therefore be used in different therapeutic applications. The present invention also relates to a pharmaceutical composition comprising, as active principle, a compound of general formula (I) as defined above, or a pharmaceutically acceptable salt of such a compound, with at least one pharmaceutically acceptable excipient. acceptable. The subject of the present invention is also, as a medicament, a compound of general formula (I) as defined above, or a pharmaceutically acceptable salt of such a compound. The present invention also relates to the use of a compound of general formula (I) as defined above or a pharmaceutically acceptable salt thereof, for preparing a medicament for treating or preventing a disease or R3N NHW R5b R4b N-

N ~ R5a. R4a disorder selected from the following diseases or disorders: cancers, proliferative tumoral diseases, non-tumorous proliferative diseases, neurodegenerative diseases, parasitic diseases, viral infections, spontaneous alopecia, alopecia induced by exogenous products, radiation-induced alopecia, autoimmune diseases, rejection of transplants, inflammatory diseases or allergies. Preferably, the present invention relates to the use of a compound of general formula (I) as defined above or a pharmaceutically acceptable salt thereof, for preparing a medicament for treating or preventing cancers. . Very preferably, the present invention relates to the use of a compound of general formula (I) as defined above or a pharmaceutically acceptable salt thereof, for preparing a medicament for treating or preventing the cancer, said cancer being selected from cancers of the colon, rectum, stomach, lungs, pancreas. kidney, testes, breast, uterus, ovary, prostate, skin, bones, spinal cord, neck, tongue, head and sarcomas, carcinomas, fibroadenomas, neuroblastomas, leukemias, melanomas. The compound of general formula (I) or its salt used according to the invention may be in the form of a solid, for example powders, granules, tablets, capsules. liposomes or suppositories. Suitable solid supports may be, for example. calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin. starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine and wax. The compound of general formula (I) or its salt used according to the invention may also be in liquid form, for example solutions, emulsions, suspensions or syrups. Suitable liquid carriers may be, for example, water, organic solvents such as glycerol or glycols, as well as their mixtures, in varying proportions, in water. The administration of a compound of general formula (I) or its salt used according to the invention or the combination according to the invention may be carried out topically, orally, parenterally. by intramuscular injection, subcutaneous etc.

The dose of a product according to the present invention, to be provided for the treatment of the diseases or disorders mentioned above, varies according to the mode of administration, the age and the body weight of the subject to be treated as well as the state of the latter, and it will ultimately be decided by the attending physician or veterinarian. Such a quantity determined by the attending physician or veterinarian is referred to herein as a "therapeutically effective amount". As an indication, the envisaged administration dose for a drug according to the invention is between 0.1 mg and 10 g depending on the type of active compound used.

EXPERIMENTAL PART The NMR analyzes of Examples 1 to 32 were carried out on a 400 MHz Bruker-10 Avance II spectrometer. The compounds are characterized by their molecular peak (MH +) determined by mass spectrometry (MS), a simple quadrupole mass spectrometer (Micromass, Platform model) equipped with an electrospray source is used with a resolution of 0.8 da at 50% of valley. For Examples 1 to 90 below, the elution conditions corresponding to the results indicated are as follows: elution with acetonitrile-water-trifluoroacetic acid 50-950-0.2 (A) for 1 minute then passage of mixing (A) with a 950-50 acetonitrile mixture (B) by a linear gradient over a period of 7.5 minutes, then eluting with pure B mixture for 2 minutes. According to the preceding definitions of the variables R1, R2, W, R3, R4a, R5a, R5a, R5b, n and q, the compounds according to the invention can be prepared according to the various procedures described above. The examples are presented to illustrate the above procedures and should in no way be considered as a limit to the scope of the invention. The terminology used for the nomenclature of the compounds below and examples is the IUPAC terminology.

EXAMPLE 1 N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N-12- (pyrimidin-2-ylamino) ethyllethane-1,2-diamine hydrochloride The compound N (2-aminoethyl) -N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methylethane-1,2-diamine (0.275 g, 0.00082 mol) prepared according to the procedure described in patent application WO 2008/152223, and the compound 2-chloropyrimidine (0.113 g: 0.00099mo1) are dissolved in 10 ml of ethanol at room temperature. Triethylamine (0.138 ml, 0.00099 mol) is added, then the reaction mixture is heated for 4 hours, brought to room temperature and then the ethanol is evaporated. The residue is taken up in water and ethyl acetate and then the aqueous phase is extracted 3 times with ethyl acetate. The organic phase is washed with a saturated solution of sodium chloride and then dried over sodium sulfate. After evaporation of the solvent on a rotary evaporator, the residual oil is chromatographed on a silica column (eluent: dichloromethane-methanol-ammonia 7N: 80-20-5) in order to obtain a yellow oil. This oil is diluted in ether (1 ml), then a solution of hydrochloric acid in ether (2N) (1.2 ml, 0.004 mol) is added, the reaction mixture is stirred for 3 hours and the solvent is then added. and the excess of acid are evaporated. 10 ml of diethyl ether are added and then the solid is sintered. After drying under vacuum at 65 ° C. a solid is obtained in the form of a light brown powder, with a yield of 10%. 1 H NMR (8 ppm, DMSO): 1.87-1.92 (m, 8H); 2.86 (s, 3H); 3.30-3.70 (m, 16H); 5.26 (s, 1H); 6.69 (si, 1H); 7.60 (sl, 1H); 8.11 (sl, 1H); 8.35 (d, 2H); 11.08 (sl, 1H); 11.75 (sl, 1H). Experimental MH + = 412.23; M theoretical = 411.29 Examples 2 and 3: N- {2- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyll-N-methyl-N ', N'-dipyridin-2- hydrochloride Ylethan-1,2-diamine and N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2- (pyridin-2-ylamino) ethyllethane-1,2 hydrochloride) N- (2-aminoethyl) -N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methylethane-1,2-diamine (0.3 g, 0.0009 mol), prepared according to the procedure described in the patent application WO 2008/152223. 2-bromopyridine compound (861_1l, 0.0009 mol), 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (22mg, 0.04mmol), Pd2 (DBA) 3 (16mg, 0.02mol) and sodium tert-butylate (0.121 g: 1.3 mmol) are dissolved in 1 ml of anhydrous toluene previously degassed. The reaction mixture is heated at 70 ° C for 2 hours, brought to room temperature and toluene is evaporated. The residue is taken up in water and ethyl acetate and then the aqueous phase is extracted 3 times with ethyl acetate. The organic phase is washed with a saturated solution of sodium chloride and then dried over sodium sulfate. After evaporation of the solvent on a rotary evaporator, the residual oil is chromatographed on a silica column (eluent: tetrahydrofuran-methanol: 95-5) in order to isolate two compounds (1) and (2), treated and then salified according to a similar procedure to that of Example 1.

Compound (1) = Example 2: N- {2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) aminoethyl-N-methyl-N ', N'-dipyridin-2-ylethane-1 hydrochloride 2-diamine 1 H-NMR (8 ppm, DMSO): 1.87-1.92 (m, 8H); 2.93 (s, 3H); 3.34-3.72 (m, 14H) 4.53 (s, 2H); 5.21 (s, 1H): 7.07 (dd, 2H); 7.21 (dd, 2H); 7.44 (t, 2H); 8.25 (sl 1H); 8.38 (d.2H); 11.32 (si, 1H); 11.79 (si, 1H).

Experimental MH + = 488.28; M = 487.32 Compound (2) = Example 3: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- [2- (pyridin-2-ylamino) hydrochloride ethyl] ethane-1,2-diamine 1 H-NMR (8 ppm, DMSO): 1.74-1.92 (m, 8H); 2.86 (s, 3H); 3.32-3.91 (m, 16H); 5.29 (st, 1H); 6.86-6.90 (m, 1H): 7.12 (d, 1H); 7.87-7.93 (m, 2H); 8.09 (st, 1H); 9.16 (si, 1H); 11.33 (sl, 1H); 11.73 (st, 1H). Experimental MH + = 411.27; M = 410.29 Example 4: N '- (4-tert-butylphenyl) -N- {2 - ((2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethy} -N-methylethane-1, 2-diamine The compound N- (2-aminoethyl) -N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methylethane-1,2-diamine (0.2 g, 0.0006 mol) prepared according to the procedure described in patent application WO 2008/152223 and the compound 1-tert-butyl-4-iodobenzene (89111, 0.0005mol) are dissolved in a mixture containing cuprous iodide (95 mg, 0.05 mmol) and cesium acetate (0.24 g, 0.00125 mol) in 3 ml of anhydrous dimethylformamide before degassing The reaction mixture is heated at 60 ° C. for 1.5 hours, brought to ambient temperature and the solvent is then evaporated. The residue is taken up in 20% aqueous ammonia solution and ethyl acetate, and then the aqueous phase is extracted 3 times with ethyl acetate.The organic phase is washed with a saturated sodium chloride solution. sodium and then dried over sodium sulphate. When the solvent is evaporated on a rotary evaporator, the residual oil is chromatographed on a silica column (eluent: 7N: 98-2 to 95-5 ammonium dichloromethane-methanol) to obtain a yellow oil with a yield of 21%. 1 H NMR (8 ppm, DMSO): 1.19 (s, 9H); 1.76-1.84 (m, 8H); 2.24 (s, 3H); 2.48-2.55 (m, 4H); 3.04 (m, 2H); 3.25-3.38 (m, 10H); 4.74 (sl, 1H); 5.05 (si, 1H); 5.92 (si, 1H); 6.48 (d, 2H); 7.05 (d, 2H).

Experimental MH + = 466.34; M = 465.36 Example 5: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2- (4-nitrophenyl) aminolethyl} ethane-1 hydrochloride The compound 5 described below was synthesized according to a method analogous to that described in Example 4, using 1-iodo-4-nitrobenzene as starting reagent to replace 2-chloropyrimidine. 1 H NMR (8 ppm DMSO): 1.85-1.93 (m, 8H); 2.86 (s, 3H); 3.27-3.73 (m.p. 16H): 5.22 (s, 1H); 6.72 (d, 2H); 7.56 (sl, 1H); 7.94-8.02 (m, 3H); 11.17 (si, 1H); 11.65 (si, 1H). Experimental MH + = 455.23: M theoretical = 454.28 Melting point: 136-148 ° C Example 6: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N-f 2 (7H-purin-6-ylamino) ethyllethane-1,2-diamine The compound 6 described below was synthesized according to a method analogous to that described in Example 1, using 6-chloropurine as replacement reagent. 2-chloropyrimidine.

1 H NMR (8 ppm DMSO): 1.75-1.83 (m, 8H); 2.27 (s, 3H); 2.49-2.64 (m, 4H); 3.58-3.60 (m, 12H); 4.69 (s, 1H); 5.88 (se, 1H); 7.34 (se, 1H); 8.05 (s, 1H); 8.17 (s, 1H); 12.87 (s, 1H). Experimental MH + = 452.37; M = 451.29 Melting point: 110-120 ° C. EXAMPLE 7 N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- (2- {14} Hydrochloride - (trifluoromethyl) pyrimidin-2-yllamino} ethyl) ethane-1,2-diamine Compound 7 described below was synthesized according to a method analogous to that described in Example 1, using as starting reagent the 4- (trifluoromethyl) pyrimidin-2-amine to replace 2-chloropyrimidine. 1 H NMR (δ ppm, DMSO): 1.84-1.94 (m, 8H); 2.86 (s, 3H); 3.25-3.72 (m, 16H); 5.27 (s, 1H); 7.04 (d 1H): 8.04 (si, 1H); 8.13 (sl, 1H); 8.63 (d, 1H); 11.14 (si, 1H); 11.79 (si, 1H).

Experimental MH + = 480.19; M = 479.27 Melting point: 139-148 ° C Example 8: N-12-1 {2- [2,6-dipyrrolidin-1-ylpyrimidin-4-yl] aminolethyl} (methyl) aminolethyl hydrochloride } -2- (pyrimidin-2-ylsulfanyl) acetamide The compound N- (2-aminoethyl) -N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methylethane-1,2-diamine (0.2 g, 0.0006 mol), prepared according to the procedure described in the patent application WO 2008/152223, the compound 2- (carboxymethylthio) pyrimidine (0.112 g, 0.00072 mol), the hydrochloride of l-ethyl- 3- [3-dimethylaminopropyl] carbodiimide (0.162 g, 0.00072 mol), the hydroxybenzotriazole compound (0.23 g, 0.00072 mol) and triethylamine (0.334 ml, 0.0014 mol) are dissolved in 1 ml of anhydrous dichloromethane. The reaction mixture is stirred at 23 ° C for 6 hours and then water and dichloromethane are added. The aqueous phase is extracted 3 times with dichloromethane. The organic phase is washed with a saturated solution of sodium chloride and then dried over sodium sulfate. After evaporation of the solvent on a rotary evaporator, the residual oil is chromatographed on a silica column (eluent: ammonia dichloromethane-methanol 7N: 97-3 to 95-5) in order to obtain a yellow oil. This oil is diluted in dichloromethane (5 ml) then a solution of hydrochloric acid in ether (2N) (1 ml, 0.003 mol) is added and the mixture is stirred for 1 hour. The solvent and the excess of acid are evaporated. 10 ml of diethyl ether are added and the solid is then sintered. After drying under vacuum, the compound is obtained in the form of a yellow powder. ¹H-NMR (8 ppm, DMSO): 1.84-1.94 (m, 8H); 2.81 (s, 3H); 3.13-3.73 (m, 16H); 3.90 (s, 2H); 5.31 (s, 1H); 7.21 (t, 1H); 8.0 (tl, 1H); 8.49 (tl, 1H); 8.61 (d.2H); 11.03 (si, 1H); 11.68 (si, 1H). Experimental MH + = 48624; M = 485.27 m.p .: 122-126 ° C Example 9: N- {2 - {(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminol ethyl} -2- (pyrimidine) hydrochloride 2-ylsulfanyl) acetamide Compound 9 described below was synthesized according to a method analogous to that described in Example 8 using N- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) as starting reagent. ) ethane-1,2-diamine replacing N- (2-aminoethyl) -N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methylethane-1,2-diamine. 1 H NMR (8 ppm, DMSO): 1.84-1.92 (m, 8H); 3.24-3.47 (m, 12H); 3.85 (2H): 5.09 (s, 1H); 7.18 (t, 1H); 7.86 (si, 111); 8.33 (si, 1H); 8.59 (d, 2H); 11.60 (si, 1H). Experimental MH + = 429.12; M = 428.21 Melting point: 80-84 ° C Example 10: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- (2-l) hydrochloride ( 5-nitropyrimidin-2-yl) aminolethyl} ethane-1,2-diamine Compound 10 described below was synthesized according to a method analogous to that described in Example 1 using 2-chloro-2 5-nitropyrimidine replacing 2-chloropyrimidine and as a reaction solvent, tetrahydrofuran. 1 H NMR (8 ppm DMSO): 1.85-1.92 (m, 8H); 2.86 (s, 3H); 3.26-3.82 (m, 16H); 5.26 (s, 1H); 8.16 (sl, 1H); 8.91 (s i, 1H); 9.05 (d, 2H); 11.35 (sl, 1H); 11.79 (if, 1H). Experimental MH + = 457.21; M = 456.27 Melting point: 161-173 ° C Example 11: N '- (6-Chloropyrimidin-4-yl) -N- {2-l (2,6-dipyrrolidin-1-ylpyriimidine) hydrochloride 4-yl) aminolethyl) -N-methylethane-1,2-diamine Compound 11 described below was synthesized according to a method analogous to that described in Example 1, using 4,6-as the starting reagent. dichloropyrimidine replacing 2-chloropyrimidine and as a reaction solvent, tetrahydrofuran. 1 H NMR (b ppm, DMSO): 1.87-1.93 (m, 8H); 2.85 (s, 3H); 3.31-3.74 (m, 16H); 4.82 (st, 1H); 5.27 (s, 1H); 6.60 (sl, 1H); 8.10 (si, 1H); 8.28 (si, 2H); 11.11 (si, 1H): 11.73 (si, 1H). MH + Experimental = 44620: M theoretical = 445.25 Melting point: 155-162 ° C Example 12: N- {2-112-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyl} (methyl The compound 12 described below was synthesized according to a method analogous to that described in Example 8, using 4-nitrobenzoic acid as the starting reagent instead of 2- (carboxymethylthio). ) pyrimidine. 1 H NMR (δ ppm, DMSO): 1.76-1.84 (m, 8H); 2.26 (s, 3H); 2.31-2.42 (m, 4H); 3.24-3.40 (m, 12H); 4.68 (s, 1H); 5.79 (st, 1H); 8.00 (d, 2H); 8.25 (d, 2H); 8.64 (tl, 1H). Experimental MH + = 483.19: M theoretical = 482.28 Melting point: 156-160 ° C Example 13: N- {2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) hydrochloride aminolethyl (meth) aminol ethyl-3- (trifluoromethyl) benzamide The compound 13 described below was synthesized according to a method analogous to that described in Example 8, using 3- (trifluoromethyl) acid as starting reagent. ) benzoic acid instead of 2- (carboxymethylthio) pyrimidine.

1 H NMR (5 ppm, DMSO): 1.74-1.84 (m, 8H); 2.81 (s, 3H); 3.17-3.68 (m, 16H); 5.19 (s, 1H); 7.64 (t, 1H); 7.84 (d 1H); 7.91 (st, 1H); 8.15-8.17 (m, 2H); 9.06 (tl, 1H); 10.90 (st, 1H); 11.54 (si, 1H).

Experimental MH + = 506.19 M theoretical = 505.28 Melting point: 131-145 ° C Example 14: N- {2 - [{2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethylhydrochloride } (methyl) aminol ethyl} -3,5-bis (trifluoromethyl) benzamide Compound 14 described below was synthesized according to a method analogous to that described in Example 8, using as starting reagent 3.5- bis (trifluoromethyl) benzoic acid to replace 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 1.83-1.91 (m, 8H); 2.89 (s, 3H); 3.25-3.75 (m, 16H); 5.28 (s, 1H); 8.05 (st, 1H); 8.32 (s, 11-1); 8.56 (s, 2H); 9.42 (tl, 1H); 11.13 (si, 1H); 11.68 (st 1H). Experimental MH + = 574.15; M = 573.26 Melting point: 131-145 ° C. Example 15: N- {2-1 {2- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyl} (methyl) aminol ethyl Hexadecanamide Compound 15 described below was synthesized according to a method analogous to that described in Example 8 using palmitic acid as starting reagent instead of 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 0.83 (sl, 3H); 1.22 (m, 24H); 1.43 (si, 2H); 1.80-1.83 (m, 8H) 1.99 (t, 2H); 2.19 (s, 311); 2.37 (tl, 2H); 2.43-2.45 (m, 2H); 3.1-3.37 (m, 12H); 4.75 (1H); 5.83 (si, 1H); 7.58 (si, 1H). Experimental MH + = 572.36; M = 571.49 Melting point: 97-100 ° C. EXAMPLE 16 N- {2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyll (methyl) aminol ethyll 4-Octylbenzamide Compound 16 described below was synthesized according to a method analogous to that described in Example 8, using 4-octylbenzoic acid as starting reagent as a substitute for 2- (carboxymethylthio) pyrimidine.

1 H NMR (8 ppm, DMSO): 0.85 (t, 3H); 1.23-1.26 (m, 10H); 1.55 (t, 2H); 1.77-1.84 (m, 8H); 2.28 (si, 3H); 2.57-2.61 (m, 6H); 3.26-3.37 (m, 12H); 4.74 (s, 1H); 5.91 (si, 1H); 7.22 (d, 2H): 7.71 (d, 2H): 8.23 (si, 1H). Experimental MH + = 550.31; M = 549.42 Melting point: 65-67 ° C Example 17: N- {2-1 {2- [2,6-dipyrrolidin-1-ylpyrimidin-4-yl] aminolethyl} (methyl) aminol ethyl The compound 17 described below was synthesized according to a method analogous to that described in Example 8, using 3-fluoro-4-nitrobenzoic acid as a starting reagent to replace 3-fluoro-4-nitrobenzamide. 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 1.86-1.90 (m, 8H); 2.49 (s, 3H); 3.29-3.50 (m.p. 16H): 4.79 (s, 1H); 7.84 (d 1H); 7.94 (d, 1H); 8.19 (t, 1H); 9.04 (si, 1H); 11.22 (si, 1H). Experimental MH + = 501.20: M theoretical = 500.27 Melting point: 180-182 ° C '(decomposition) Example 18: N- {2-1 {2-I (2,6-Dipyrrolidin-1-ylpyrimidine) hydrochloride 4-yl) aminolethyl (methyl) aminol ethyl-4-nitro-3- (trifluoromethyl) benzamide Compound 18 described below was synthesized according to a method analogous to that described in Example 8 using as a reagent of 4-nitro-3- (trifloromethyl) benzoic acid is substituted for 2- (carboxymethylthio) pyrimidine.

1 H-NMR (8 ppm, DMSO): 1.82-1.97 (m, 8H); 2.88 (s, 3H); 3.24-3.46 (m, 12H); 3.70-3.76 (m, 4H); 5.26 (s, III); 7.96 (sl, 1H); 8.26 (d, 1H); 8.46 (d, 1H); 8.48 (s, 1H); 9.41 (tl, 1H); 11.04 (si, 1H); 11.59 (sl, 1H). Experimental MH + = 551.17 M theoretical = 550.26 Melting point: 133-135 ° C Example 19: N- {2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethylhydrochloride } (methyl) aminol ethyl} -4-fluoro-3-nitrobenzamide Compound 19 described below was synthesized according to a method analogous to that described in Example 8 using 4-fluorinated acid as starting reagent. 3-nitrobenzoic acid replacing 2- (carhoxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 1.82-1.87 (m, 8H); 2.88 (s, 3H); 3.26-3.45 (m, 12H); 3.68-3.74 (m, 4H); 5.22 (I, I); 7.71 (dd, 1H); 7.97 (sl, 1H); 8.36-8.39 (m, 1H); 8.66 (d, 1H) 9.25 (tl, 1H); 10.97 (si, 1 FI); 11.58 (si, 1H). Experimental MH + = 501.16; M = 500.58 m.p .: 121-136 ° C Example 20: Methyl 4 - ({2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyl} hydrochloride ( The compound 20 described below was synthesized according to a method analogous to that described in Example 8 using 1-methyl-2-nitroterephthalate as replacement for the starting compound. 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 1.81-1.86 (m, 8H); 2.88 (s, 3H); 3.24-3.45 (m, 12H): 3.68-3.75 (m, 4H); 3.87 (s, 311); 5.23 (s, 1H); 7.95 (d, 1H); 8.00 (si, 1H); 8.35 (d, 1H); 8.55 (s, 1H); 9.32 (tl, 1H); 10.99 (si, 1H); 11.61 (sl, 1H). Experimental MH + = 541.19: M theoretical = 540.28 Melting point: 121-136 ° C Example 21: 4-butoxy-N- {2-1 {2- (2,6-dipyrrolidin-1-ylpyrimidin-4-) yl) aminolethyl} (methyl) aminolethyl} benzamide Compound 21 described below was synthesized according to a method analogous to that described in Example 8, using 4-butoxybenzoic acid as starting reagent to replace 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm DMSO): 0.93 (t, 3H); 1.38-1.47 (m, 2H); 1.66-1.70 (m, 2H); 1.71-1.84 (m, 8H); 2.24 (s, 3H); 2.31-2.66 (m, 4H); 3.24-3.37 (m, 12H); 3.99 (m, 2H); 4.71 (s, 1H) 5.85 (si, 1H); 6.92 (d, 211); 7.76 (d, 2H); 8.14 (t, 1H).

MH + experimental = 510.24; M = 409.35 Melting point: 99-101 ° C Example 22: N- {2-1 {2- [2,6-Dipyrrolidin-1-ylpyrimidin-4-yl] aminolethyl} (methyl) aminol ethyl } -5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide Compound 22 described below was synthesized according to a method analogous to that described in Example 8 using starting reagent 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenecarboxylic acid to replace 2- (carboxymethylthio) pyriniidine.

1 H NMR (8 ppm, DMSO): 1.25 (s, 12H); 1.64 (s, 4H); 1.77-1.84 (m, 8H); 2.27 (s, 3H): 2.49-2.54 (m, 4H); 3.25-3.40 (m, 12H); 4.75 (s, 1H); 5.90 (si, 1H); 7.34 (d 1H); 7.54 (d, 1H); 7.77 (s, 1H); 8.26 (tl, 1H). Experimental MH + = 548.28 M theoretical = 547.40 Melting point: 141-146 ° C (decomposition) Example 23: N- {2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) aminolethyl (methyl) aminol ethyl) -2,3,4,5,6-pentafluorobenzamide Compound 23 described below was synthesized according to a method analogous to that described in Example 8, using as starting reagent the pentafluorobenzoic acid to replace 2- (carboxymethylthio) pyrimidine.

1 H NMR (8 ppm, DMSO): 1.71 (m, 8H); 2.32 (s, 3H); 2.59 (m, 4H); 3.29-3.38 (m, 12H); 4.82 (si, 1H): 8.97 (si 1H): 11.38 (si, 1H). Experimental MH + = 528.14 M theoretical = 527.24 Melting point: 182-195 ° C (decomposition) Example 24: 4- (Dipropylsulfamoyl) -N- {2-1 {2-1 (2,6-dipyrrolidine) hydrochloride 1H-ylpyrimidin-4-yl) aminolethyl} (methyl) aminolethyllbenzamide Compound 24 described below was synthesized according to a method analogous to that described in Example 8 using 4- (dipropylsulfamoyl) benzoic acid as starting reagent. replacing 2- (carboxymethylthio) pyrimidine. 1 H NMR (8 ppm, DMSO): 0.73 (t, 6H); 1.41 (t, 4H); 1.74-1.79 (m, 8H); 2.81 (s, 3H); 2.94-2.98 (m, 4H); 3.18-3.40 (m, 12H); 3.60-3.69 (m, 4H); 5.21 (1H); 7.78 (d, 2H): 7.98 (si, 1H): 8.03 (d, 211): 9.05 (br, 1H); 10.96 (si, 1H); 11.61 (si, 1H). Experimental MH + = 601.21 M theoretical = 600.36 Melting point: 130-144 ° C Example 25: 4-Cyano-N- {2-1 {2-1 (2,6-dipyrrolidin-1-ylpyrimidine) hydrochloride 4-yl) aminol ethyl (methyl) aminolethyl) benzamide The compound described below was synthesized according to a method analogous to that described in Example 8 using as starting reagent 4-cyanobenzoic acid to replace 2- (carhoxymethylthio) pyrimidine. 1 H-NMR (8 ppm, DMSO): 1.84-1.97 (m, 81-1); 2.88 (s, 3H); 3.26-3.46 (m, 12H); 3.67-3.73 (m, 4H); 5.23 (1H); 7.93 (d, 2H); 7.98 (si, 1H); 8.07 (d, 2H); 9.20 (Si, 1H); 11.00 (si, 1H); 11.61 (si, 1H). Experimental MH + = 463.17 M theoretical = 462.29 Melting point: 131-168 ° C Example 26: N'-1,3-henzothiazol-2-yl-N- {2-1 (2,6-dipyrrolidin-1-one) Ylpyrimidin-4-yl) aminolethyl} -N-methylethane-1,2-diamine Compound 26 described below was synthesized according to a method analogous to that described in Example 1, using 2-bromo as starting reagent. -1,3 benzothiazole to replace 2-chloropyrimidine. 1 H-NMR (8 ppm, DMSO): 1.82 (m, 8H); 2.49-2.53 (m, 4H); 2.53 (s, 3H); 3.34-3.40 (m, 12H); 4.78 (si, 1H); 7.00 (dd 1H); 7.20 (dd, 1H); 7.35 (d, 1H); 7.64 (d 1H); 7.98 (st, 1H); 8.29 (si, 1H).

Experimental MH + = 46723: M theoretical = 466.26 Example 27: N, N'-bis (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) pentane-1,5-diamine The compound 4-chloro-2.6- dipyrrolidin-1-ylpyrimidine (1g; 0.004 mol), prepared according to the procedure described in the patent application WO 2008/152223, the compound 1,5-diaminopentane (0.1 18 ml: 0.001 mol) and the triethylamine compound (0 , 56m1; 0.004mo1) are dissolved in a sealed glass tube suitable for microwave heating. The mixture is heated for 1 hour at 190 ° C in a microwave oven (Biotage, Emrys Optimiser), then taken up in water and ethyl acetate. The aqueous phase is extracted 3 times with ethyl acetate. The organic phase is washed with a 1M citric acid solution. then the aqueous phase is neutralized with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is removed on a rotary evaporator. The resulting oil solidifies over time to form the solid compound as a pink powder with a yield of 10%. 1 H-NMR (δ ppm DMSO): 1.19-1.30 (m, 2H); 1.41-1.48 (m, 4H); 1.73-1.84 (m, 16H); 3.07-3.30 (m, 20H); 4.64 (s, 2H); 5.93 (sl, 2H) MH + experimental = 535.30; M = 534.75 Melting point: 65-78 ° C. Example 28: N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N- {2-I (2,6-dipyrrolidinone) 1-ylpyrimidin-4-yl) aminolethyl} -N-methylethane-1,2-diamine Compound 28 described below was synthesized according to a method analogous to that described in Example 27, using as starting reagent N - (2-aminoethyl) -N-methylethane-1,2-diamine replacing the 1,5-diaminopentane compound. 1 H NMR (8 ppm, DMSO): 1.70-1.90 (m, 16H); 2.5-2.8 (m, 3H); 3.1-3.4 (m, 24H); 4.64 (s, 2H); 6.3 (sl, 2H) MH + experimental = 550.34; M = 549.40 mp: 138-140 ° C Example 29: N '- (9-Benzyl-9H-purin-6-yl) -N- {2-1 (2,6-dipyrrolidin-1) Ypyrimidin-4-yl) aminolethyl) -N-methylethane-1,2-diamine Compound 29 described below was synthesized according to a method analogous to that described in Example 1, using 9-methoxy-1,2-diamine as the starting reagent. benzyl-6-chloro-9H-purine prepared as described in Journal of Medicinal Chemistry (2005), 48 (3), 710-22, replacing 2-chloropyrimidine. 1 H NMR (δ ppm, DMSO): 1.73-1.83 (m, 8H); 2.24 (s, 3H); 2.49-2.63 (m, 4H); 3.24-3.57 (m, 12H); 4.70 (s, 1H): 5.36 (s, 2H); 5.87 (se, 1H); 7.25-7.34 (m, 5H); 7.49 (se, 1H): 8.21 (se, 1H); 8.23 (s, 111).

Experimental MH + = 542.43; M = 541.34 Melting point: 78-80 ° C Example 30: N '- (7-Benzyl-7H-purin-6-yl) -N- {2 - [(2,6-dipyrrolidin-1-one) Ylpyrimidin-4-yl) aminolethyl} -N-methylethane-1,2-diamine Compound 30 described below was synthesized according to a method analogous to that described in Example 1 using 7-benzyl as starting reagent. 6-chloro-7H-purine prepared as described in Journal of Medicinal Chemistry (2005), 48 (3), 10-22, to replace 2-chloropyrimidine, 1H-NMR (8 ppm, DMSO). ): 1.75-1.84 (m, 8H), 2.18 (s, 3H), 2.49-2.63 (m, 4H), 3.22-3.46 (m, 12H); 4.69 (s, 1H): 5.56 (s, 2H), 5.87 (se, 1H), 6.2 (se, 1H), 7.10-7.34 (m, 5H); , 24 (s, 1H), 8.39 (se, 1H) MH + experimental = 542.39: M theoretical = 541.34 Melting point: 80 ° C Example 31: N '- (2,6-Dipyrrolidin-1-ylpyrimidine) 4-yl) -N-methyl-N- {2 - [(9-methyl-9H-purin-6-yl) aminolethyllethane-1,2-diamine Compound 31 described below was synthesized according to a similar method to that described in Example 1 using as starting reagent 6-chloro-9-methyl-9H-purine prepared as described in Bioorganic & Medicinal Chemistry (2004), 12 (1), 139-149, replacing the 2 -chloropyrimidine.

1 H NMR (8 ppm, DMSO): 1.76-1.84 (m, 81-1); 2.21 (s, 3H); 2.49-2.63 (m, 4H); 3.24-3.57 (m, 12H): 3.71 (s, 3H); 4.70 (s, 1H); 5.87 (se, 1H); 7.42 (se, 1H); 8.06 (s, 1H); 8.21 (se, 1H) MH + experimental = 465.31 M theoretical = 466.36 Melting point: 85-90 ° C Example 32: N6-12-I {2 - [(2,6-dipyrrolidin-1-ylpyrimidin) 4-yl) Aminolethyl (methyl) aminolethyl) -7H-purine-2,6-diamine The compound 32 described below was synthesized according to a method analogous to that described in Example 1, using as starting reagent the 6-chloro-7H-purin-2-amine to replace 2-chloropyrimidine.

1 H NMR (8 ppm, DMSO): 1.75-1.83 (m, 8H); 2.27 (s, 3H); 2.49-2.64 (m, 4H): 3.58-3.60 (m, 12H): 4.15 (m, 2H): 4.69 (s, 1H); 5.88 (se, 1H); 7.34 (se, 1H); 8.05 (s, 1H); 12.87 (s, 1H). Experimental MH + = 465.31: M theoretical = 466.30 Melting point: 120 ° C STUDY OF THE COMPOUNDS ACCORDING TO THE INVENTION: A- Pharmacological study Test protocols i) Measurement of the phosphatase activity of the purified Cdc25C recombinant enzyme : The phosphatase activity of the MBP-Cdc25C protein is evaluated by the dephosphorylation of 3-O-methylfluorescein-phosphate (OMFP) to 3-O-methylfluorescein (OMF) with a determination of the fluorescence at 475 nm of the reaction product . This test makes it possible to identify inhibitors of the recombinant Cdc25 enzyme. The preparation of the MBP-Cdc25C fusion protein is described in PCT patent application WO 01/44467. The reaction is carried out in 384 well plate format in a final volume of 50 μl. The MBP-Cdc25C protein (prepared as described above) is stored in the following elution buffer: 20 mM Tris-HCl pH 7.4; 250 mM NaCl; 1 mM EDTA; 1mM dithiothreitol (DTT); 10 mM maltose. It is diluted to a concentration of 60 μM in the following reaction buffer: 50 mM Tris-HCl pH 8.2; 50 mM NaCl; 1 mM DTT; 20% glycerol. The measurement of the background noise is carried out with the buffer without the addition of the enzyme. The products are tested at decreasing concentrations starting from 40 M. The reaction is initiated by the addition of a final 500 M OMFP solution (prepared extemporaneously from a 12.5 mM stock solution in 100% DMSO (Sigma # M2629)). After 4 hours at 30 ° C. in a 384-well single-use plate, the fluorescence measured at OD 475 nm is read using a Victor2 plate reader (EGGWallac). Determination of the concentration inhibiting the enzymatic reaction by 50% is calculated from three independent experiments. Only the values contained in the linear part of the sigmoid are retained for the linear regression analysis. ii) Characterization of the anti-proliferative activity: By way of example. the effect of a treatment on two human cell lines Mia-Paca2 and DU145 by the compounds of the examples described above will be studied. Cell lines DU145 (human prostate cancer cells) and Mia-PaCa2 (human pancreatic cancer cells) were purchased from American Tissue Culture Collection (Rockville, Maryland, USA). Cells placed in 80 L of modified Dulbecco's Eagle medium (Gibco-Brl, Cergy-Pontoise, France) supplemented with 10% heat inactivated calf fetal serum (Gibco-Brl, Cergy-Pontoise, France), 50,000 units / 1 penicillin and 50 mg / 1 streptomycin (Gibco-Brl, Cergy-Pontoise, France), and 2 mM glutamine (Gibco-Brl, Cergy-Pontoise, France) were inoculated on a 96-well plate at day 0. The cells were treated on day 1 for 96 hours with increasing concentrations of each of the test compounds up to 10MM. At the end of this period, quantification of cell proliferation is evaluated by colorimetric assay based on cleavage of tetrazolium salt WST1 by mitochondrial dehydrogenases in viable cells leading to formazan formation (Boehringer Mannheim, Meylan, France). ). These tests are performed in duplicate with 8 determinations per concentration tested. For each test compound, the values included in the linear part of the sigmoid were retained for a linear regression analysis and used to estimate the IC50 inhibitory concentration. The products are solubilized in 10-2 M dimethylsulfoxide (DMSO) and used in culture with 0.1% DMSO in the final.

Results of the Tests: Results on the CDC25 Enzyme The compounds of the examples presented above have an IC 50 less than or equal to 40 M on the activity of the purified Cde25-C recombinant enzyme.

Among these compounds, Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18. 19. 20, 21. 22. 23, 24. 25, 26. 27. 28, 29, 30, 31 and 32 have an IC50 less than or equal to 10 M. Among these, examples 2, 5, 6, 7, 8, 9, 11, 12, 17 , 19, 20, 21, 22, 23, 25, 26, 27, 28, 29. 30, 31 and 32 have an IC50 less than or equal to 2000 nM.

Of these, Examples 6, 11, 17, 21, 27, 28, 29, 30 and 31 have an IC 50 less than or equal to 1000 nM.

Claims (4)

1. Compound of general formula (I) R4b R5b N R4a, R1 NNN n W qN 1 R5a R3 R2 (1) in racemic, enantiomeric form or any combination thereof, wherein: R1 represents one the following radicals: aryl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl. aryl, alkylaminosulfonyl, aminosulfonyl. amino. alkylamino. dialkylamino, aralkyl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl. dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl. amino, alkylamino, dialkylamino, heteroaryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy. cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, heteroarylalkyl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, a radical of formula: R4b ,,, R5b N is a radical of formula ùCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical containing from 1 to 3 carbon atoms or a heteroaryl radical optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino; W represents NR6, CR6R7, oxygen or sulfur; R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a, R4b, R5a and R5b independently represent a hydrogen atom, an alkyl, aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl radical; or R4a and R5a and / or R4b and R5b form together with the nitrogen atom to which they are attached a heterocycloalkyl radical R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, aralkyl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl. alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino. heteroarylalkyl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof; it being understood that R2 represents a heteroaryl radical only if R1 also represents this same heteroaryl radical. 2. Compound according to claim 1, characterized in that R1 does not represent a -COR8 radical. 3. Compound according to claim 1 characterized in that R1 represents a radical - COR8. 5. Compound according to one of claims 1 to 3 characterized in that R4a and R5a, and R4b and R5b, together with the nitrogen atom to which they are attached form a heterocycloalkyl radical. 6. Compound according to rune of claims 1 to 4 characterized in that W represents - NR6-. 6. Compound according to rune of claims 1 to 4 characterized in that W represents - CR6R7-.107. Compound according to claim 1 characterized in that RI represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl. dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, heteroaryl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl , aminosulfonyl, amino, alkylamino, dialkylamino, a radical of formula: R4b-R5bNNR4aNR5a a radical of formula ùCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical containing from 1 to 3 carbon atoms or a heteroaryl radical optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino; W represents ùNR6ù. wherein R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a, R4b, R5a and R5b independently represent a hydrogen atom, an alkyl group, an aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl group; or R4a and R5a and / or R4b and R5b together with the nitrogen atom to which they are attached a heterocycloalkyl radical R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl , nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl. amino, alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof. 8. Compound according to one of claims 1 or 7 characterized in that RI represents one of the following radicals: aryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano , alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, heteroaryl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, a radical of formula: ## STR2 ## a radical of formula ## STR5 ## R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6 0, CR 6 R 7 0; R6 and R7 independently represent a hydrogen atom or an alkyl radical: n or q are integers between 0 and 6 inclusive, provided that n and q are not 0 at the same time: R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and R4b and RSb, together with the nitrogen atom to which they are attached, form a heterocycloalkyl radical R8 represents one of the following radicals: aryl substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl. a radical of formula: or a pharmaceutically acceptable salt thereof. Compound according to one of claims 1 or 7 to 8, characterized in that R1 represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino. heteroaryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy. cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino. alkylamino, dialkylamino, a radical of formula: R4b ~, R5b N N R4a ~ n N N R5a a radical of formula ùCOR8; R2 represents a hydrogen atom, a linear or branched alkyl radical having from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6, R 6 R 7 R 6, R 6 and R 7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and R4b and R5b. form together with the nitrogen atom to which they are attached a heterocycloalkyl radical: R8 represents one of the following radicals: aryl substituted by one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, aryl, alkylaminosulfonyl, aminosulfonyl, amino, alkylamino, dialkylamino, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl, a radical of formula: or a pharmaceutically acceptable salt thereof. 10. Compound according to one of claims 1 or 7 to 9 characterized in that RI represents one of the following radicals: aryl optionally substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy cyano, alkoxycarbonyl, dialkylaminosulfonyl. aralkyl, heteroaryl optionally substituted by one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, a radical of formula: R4b ,, R5b NN R4a ~ n N R5a radical of formula: ## STR1 ## R2 represents a hydrogen atom, a linear or branched alkyl radical containing from 1 to 3 carbon atoms or a heteroaryl radical; W represents NR 6 0, CR 6 R 7 0; R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom or an alkyl radical; R4a and R5a, and R4b and R5b. form together with the nitrogen atom to which they are attached a heterocycloalkyl radical; R8 represents one of the following radicals: aryl substituted with one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, aralkyl, alkyl containing from 1 to 15 carbon atoms, heteroarylthioalkyl a radical of formula: or a pharmaceutically acceptable salt thereof. 11. Compound according to one of claims 1 or 7 to 10, characterized in that R1 represents one of the following radicals: aryl optionally substituted with one or more identical or different groups chosen from alkyl, nitro, optionally substituted heteroaryl by one or more identical or different groups chosen from alkyl, haloalkyl, nitro, halo, aralkyl, a radical of formula: R4b, R5bNNR4aNNR5a a radical of formula ## STR3 ## R2 represents a hydrogen atom, or a heteroaryl radical; W represents NR 6 0, CR 6 R 7 0; R6 and R7 independently represent a hydrogen atom or an alkyl radical; n or q are integers between 0 and 6 inclusive with the proviso that n and q are not 0 at the same time; R3 represents a hydrogen atom; R4a and R5a, and R4b and R5b together with the nitrogen atom to which they are attached form a heterocycloalkyl radical; R8 represents one of the following radicals: aryl substituted with one or more identical or different groups selected from alkyl, haloalkyl, nitro, halo, alkoxy, cyano, alkoxycarbonyl, dialkylaminosulfonyl, alkyl having 1 to 15 carbon atoms, heteroarylthioalkyl. A radical of formula: or a pharmaceutically acceptable salt thereof. 12. Compound according to one of claims 1 to 11 characterized in that one or more of the following proposals is satisfied: the term heterocycloalkyl denotes a pyrrolidine or piperidine, the term aryl represents the phenyl radical, the term aralkyl represents the benzyl radical, the term heteroaryl represents a pyridinyl, pyrimidinyl, purinyl or benzothiazolyl radical, and the heteroarylthioalkyl group is the pyrimidinylthiomethyl group, or a pharmaceutically acceptable salt thereof. 13. Compound of general formula (I) chosen from one of the following compounds: N '- (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- [2- (pyrimidin-2) -ylamino) ethyl] ethane-1,2-diamine; N- {2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methyl-N ', N'-dipyridin-2-ylethan-1,2-diamine: N' (2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) -N-methyl-N- [2- (pyridin-2-ylamino) ethyl] ethane-1,2-diamine; N '- (4-tert-butylphenyl) -N-2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl] -N-methylethane-1,2-diamine: N' - ( 2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2 - [(4-nitrophenyl) amino] ethyl} ethane-1,2-diamine: N '- (2,6- dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- [2- (7H-purin-6-ylamino) ethyl] ethane-1,2-diamine; N '- (2,6-dipyrrolidine) -ylpyrimidin-4-yl) -N-methyl-N- (2 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} ethyl) ethane-1,2-diamine; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -2- (pyrimidin-2-ylsulfanyl) acetamide; N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -2- (pyrimidin-2-ylsulfanyl) acetamide; N '- (2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) -N-methyl-N- {2 - [(5-nitropyrimidin-2-yl) amino] ethyl} ethane-1,2-diamine ; N '- (6-chloropyrimidin-4-yl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-10-methylethane-1,2-diamine N - {2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -4-nitrobenzamide; N- {2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -3- (trifluoromethyl) benzamide N- {2 - [2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl] (methyl) amino] ethyl] -3,5-bis (trifluoromethyl) benzamide N- {2 - [{2 - [(2 6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl] (methyl) amino] ethyl} hexadecanamide; N- {2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -4-20 octylbenzamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl] -3-fluoro-4-nitrobenzamide; N- {2- [12 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -4-nitro-3- (trifluoromethyl) benzamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl] -4-fluoro-3-nitrobenzamide; methyl 4 - ({2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} carbamoyl) -2-nitrobenzoate; 4-butoxy-N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} benzamide; N- {2 - [{2 - [(2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene -2-carboxamide; N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl] -2,3,4,5,6-pentafluorobenzamide; 4- (dipropylsulfamoyl) -N- {2- [2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} benzamide; 4-cyano-N- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} benzamide; N1,3-benzothiazol-2-yl-N-2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl) -N-methylethane-1,2-diamine; N, N'-bis (2,6-dipyrrolidin-1-ylpyrimidin-4-yl) pentane-1,5-diamine; N '- (2,6-Dipyrrolidin-1-yl) pyrimidin-4-yl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methylethane 1,2-diamine; N '- (9-Benzyl-9H-purin-6-yl) -N- {2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} -N-methylethane-1,2 -diamine; N '- (7-Benzyl-7H-purin-6-yl) -N- {2 - [(2,6-dipyrrolidin-1-yl) pyrimidin-4-yl) amino] ethyl} -N-methylethane-1. 2-diamine; N '- (2,6-Dipyrrolidin-1-ylpyrimidin-4-yl) -N-methyl-N- {2 - [(9-methyl-9H-purin-6-yl) amino] ethyl} ethane-1 2-diamine; N6- {2 - [{2 - [(2,6-dipyrrolidin-1-ylpyrimidin-4-yl) amino] ethyl} (methyl) amino] ethyl} -7H-purine-2,6-diamine; or a pharmaceutically acceptable salt thereof. 14. Process for the preparation of a compound of general formula (I) as defined in claim 1, characterized in that this compound is prepared: - either from the compound of general formula (I int) R5b R4b N ( I int) in which R2, R3, R4a, R5a, R4b, R5b, W, n and q are as defined in claim 1 and with which: a) a compound of the general formula Rl-Z 'is reacted ( VI) in which Z 'represents a halogen atom and R1 represents an aryl, aralkyl, heteroaryl or heteroarylalkyl radical to yield the compound of general formula (Ia), R5b R4b ## STR2 ## R4a R3 is a compound of general formula (I) wherein R1 is aryl, aralkyl, heteroaryl or heteroarylalkyl, or b) a compound of the general formula R8CO2- (VII) or R8COOH (VIII) wherein R8 is as defined in claim 1 and Z "represents a halogen atom to yield the compound of formulas wherein R 1 is a compound of the general formula (I) in which R 1 is -COR - from the compound of the general formula (I int) in which R 1 is a compound of the general formula (I) in which R3, R4a, R5a, R4b, R5b, W, n and q are as defined in claim 1 and R2 is a hydrogen atom, with which a compound of the general formula Het-Z '(VI Het) is reacted; in which Het and Z 'represent respectively a heteroayl and a halogen atom, to give the compound of general formula (Ie), R5b R4b' N 'N' \\ q N, Het IH and R5a compound of general formula (I) wherein R2 and R1 are both identical heteroaryl radicals; or from the intermediate of general formula (IV) in which R4a, R5a. R4h. R5b are as defined in claim 1 and Z "represents a halogen atom, with which a compound of the general formula (VII) R3j 7 R2 n WNH is reacted withNH10 (VII) in which W, R2, R3 , n and q are as defined in claim 1 to yield the compound of general formula (Id) R5b R4b R4a 7 R5a N -N 1N.NN N NN / ~ .nw N 'R4b R4a R3 (Id) R2 R5a compound of the general formula (1) in which R 1 represents a diaminopyrimidine radical 15. A pharmaceutical composition comprising, as active ingredient, a compound of the general formula (I) according to one of claims 1 to 13 or a pharmaceutically acceptable salt thereof. one such compound with at least one pharmaceutically acceptable excipient R5a16 As a medicament, a compound of the general formula (I) according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof. Use of a compound of general formula (I) according to one of the claims 1 to 13 or a pharmaceutically acceptable salt thereof, for preparing a medicament for treating or preventing a disease or a disorder selected from the following diseases or disorders: cancers, proliferative tumoral diseases, diseases proliferative non-tumors, neurodegenerative diseases, parasitic diseases, viral infections, spontaneous alopecia, alopecia induced by exogenous products, radiation-induced alopecia, autoimmune diseases, rejection of transplants, diseases inflammatory or allergies. 18. Use according to claim 18, characterized in that the medicament prepared is intended to treat or prevent cancers. 19. Use according to claim 18, characterized in that the cancers to be treated or prevented are selected from cancers of the colon, rectum, stomach, lungs, pancreas, kidney, testes, breast. , uterus, ovary, prostate, skin, bones, spinal cord, neck, tongue, head as well as sarcomas, carcinomas, fibroadenomas, neuroblastomas , leukemias, melanomas.