NO842636L - Analogifremgangsmaate for fremstilling av terapeutisk aktive difenylazometinderivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive difenylazometinderivaterInfo
- Publication number
- NO842636L NO842636L NO842636A NO842636A NO842636L NO 842636 L NO842636 L NO 842636L NO 842636 A NO842636 A NO 842636A NO 842636 A NO842636 A NO 842636A NO 842636 L NO842636 L NO 842636L
- Authority
- NO
- Norway
- Prior art keywords
- derivatives
- preparation
- compounds
- difenylazometin
- imidazolyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 18
- -1 nitro, cyano, hydroxy, methoxy Chemical group 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229960002895 phenylbutazone Drugs 0.000 description 5
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 4
- 208000000718 duodenal ulcer Diseases 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010042220 Stress ulcer Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000767 anti-ulcer Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229940024874 benzophenone Drugs 0.000 description 2
- 239000012965 benzophenone Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- GBQHJGZKBNIMOF-UHFFFAOYSA-N (2-bromophenyl)-(5-chloro-2-hydroxyphenyl)methanone Chemical compound OC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Br GBQHJGZKBNIMOF-UHFFFAOYSA-N 0.000 description 1
- OSXVZDOVYCTYCW-UHFFFAOYSA-N (5-chloro-2-hydroxyphenyl)-(2-chlorophenyl)methanone Chemical compound OC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl OSXVZDOVYCTYCW-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- QQCSTHSPZISTMZ-UHFFFAOYSA-N Cl.Cl.N1C=NC(=C1)NC Chemical compound Cl.Cl.N1C=NC(=C1)NC QQCSTHSPZISTMZ-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000003374 anti-dyskinetic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229960000645 histamine hydrochloride Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Foreliggende oppfinnelse vedrører en analogifremgangsmåte for fremstilling av terapeutisk aktive difenylazometinderivater med formel I
hvori
X^, X3°9X4uavhengig av hverandre står for hydrogen, halogen, nitro, cyano, hydroksy, metoksy,
C til C^-alkyl, allyl eller fenyl, og
- R representerer lH-2-imidazolyl og n er 1, eller
- R representerer lH-4-imidazolyl og n er 1 eller 2,
og det karakteristiske ved oppfinnelsen er at et benzo-fenon med formel II
hvori X^, % 2 > ^3°9^4nar den ovennevnte betyd-ninfg, omsettes med en forbindelse med formel III
H„N(CH0) R (<I>II)
l Zn
hvori R og n har den ovennevnte betydning, eventuelt i form av hydrokloridet.
Disse trekk ved oppfinnelsen fremgår av patentkravet.
Reaksjonen mellom benzofenonet (II) og forbindelsen (III), eventuelt i form av hydrokloridet, gjennomføres i et løsningsmiddel som metanol, etanol eller toluen, i nærvær av en base som natriumbikarbonat, Natriumkarbonat, natriummetylat eller etylat, ved en temperatur fra 20 til 110°C.
Utgangsforbindelsene (III) fremstilles fra forbindelser som er beskrevet i litteraturen ved hjelp av tidligere kjente metoder beskrevet i litteraturen.
Mikroanalyser og spektra IR og RMN bekrefter strukturen av forbindelsene.
EKSEMPEL 1.
4-klor-2 Jj 2-klorf enyl) lH-4-imidazolyl)
metyl^j iminoj. metylj - fenol.
X1=4-C1, X2=H, X3=2-C1, n=l, R=lH-4-imidazolylj
I en Erlenmeyerkolbe innføres 2,67 g (0,009 mol)
(5-klor-2-hydroksy-fenyl) (2-klor-fenyl) metanon,
2,21 g (0,013 mol) 4-imidazolyl-metylamin-di-hydroklorid, 2,2 g (0,026 mol) NaHCC>3og 20 ml absolutt etanol. Blandingen holdes på tilbakeløpstemperaturen i 24 timer og reaksjonsblandingen inndampes til tørrhet, resten opptas i vann og metylenklorid. Uoppløselig substans frafiltreres og vaskes flere ganger med eter. Man oppnår et gult fast stoff. Den organiske fase vaskes med vann, tørkes over MgSO^og inndampes. Man oppnår et gult fast stoff som
er identisk med det foregående.
EKSEMPEL 2.
4-klor-2 jT(2-brom-f enyl) ^2 (lH-4-imidazolyl-
etyl^J imino^j- metylj - fenol.
X1=4-C1,X2=H,X3=2-Br, n=2, R=lH-4-imidazolylj
I en 500 ml rundkolbe innføres 10,3 g (5-klor-2-hydroksy-fenyl) (2-brom-fenyl) metanon og 250 ml metanol og der-etter tilsette 6,15 g histamin-hydroklorid, og 3,6 g natriummetylat. Blandingen inndampes til tørrhet, til-settes 250 ml etanol og inndampes på nytt til tørrhet. Resten opptas i kloroform, kloroformfasen vaskes med vann, blandingen dekanteres og den separerte organiske fase tørkes over MgSC>4. Faststoffet frafiltreres på glass-filter. Filtratet inndampes til tørrhet og produktet krystalliseres fra petroleter. Etter omkrystallisering tørkes i eksikkator.
Følgende forbindelser fremstilles i henhold til oppfinnelsen, se tabellen.
De ved oppfinnelsen fremstillbare forbindelser ble under-kastet farmakologiske forsøk. Deres analgetiske virkning ble påvist ved testen til Koster et Al ("writhing test" ved hjelp av eddiksyre i mus), Fed. Proe, 18, 412, 1959 .
Fastende mus tilføres oralt forbindelsen som skal testes
i oppløsning i "Tween 80" 1 %, i mengde 0,2 ml pr. 20 g kroppsvekt. Etter 30 minutter tilføres eddiksyre (0,6 % oppløsning i blandingen av karboksy-metyl-cellulose) og "Tween 80" i mengde 10 ml pr. kg kroppsvekt tilført intra-peritonealt. Man noterer det totale antall vridninger i løpet av 15 minutter.
Man bestemmer den prosentvise beskyttelse i forhold til en prøvegruppe og bestemmer AD 50 på grafisk måte (dose som beskytter 50 % av dyrene).
AD 50 av de ved oppfinnelsen fremstillbare forbindelser er fra 2 til 200 mg/kg p.o.
Forbindelsene har likeledes en antidepressiv, anti-dyskinetisk, antiulcerøs virkning og nedsetter sekre-sjonen av mavesyre.
Den antiulcerøse virkning av forbindelsene ble påvist ved tester med stress-ulcer og ulcer indusert med fenylbutazon.
Stress- ulcer.
Den anvendte teknikk er utviklet av Senay og Levine,
Proe. Soc. Exp. Biol. 1967, 124, 1221-1223, Peptic Ulcers. Utgitt av C.J. Pfeifer, side 92 - 97, med Wistar hundrotter som veide 180 - 210 g, fastende etter 20 timer, fordelt i tilfeldige grupper.
Dyrene settes inn i sylindriske bur på 20 cm x 5 cm og anbringes i et koldt rom hvor temperaturen holdes ved 2 -4°C.
Forbindelsene som testes tilføres p.o. i mengder på 10,
30 og 100 mg/kg umiddelbart før de anbringes i burene og kontrollrottene mottar bare placebo.
To timer senere avlives dyrene ved innånding av kloroform.
Mavene tas ut og uleerasjonsgraden bestemmes.
De ved oppfinnelsen fremstillbare forbindelser nedsetter tydelig forekomsten av stress-ulcer (opptil 92 %).
Ulcer indusert med fenylbutazon.
Testen gjennomføres med Wistar hunrotter som veide
180 - 210 g som var fastende etter 20 timer, og fordelt i tilfeldige grupper.
Ulcere frembringes ved oral tilførsel av fenylbutazon i molar oppløsning av NaOH i doser 200 mg/kg.
Forbindelsene som studeres tilføres p.o. i mengde på 10, 30 eller 100 mg/kg, 30 minutter før tilførsel av fenylbutazon idet kontrolldyrene bare mottar placebo.
To timer etter tilførsel av det ulcerigene middel avlives dyrene ved innånding av kloroform.
Mavene tas tas ut og ulcerasjonsgraden bestemmes.
De ved oppfinnelsen fremstillbare forbindelser nedsetter tydelig ulcer indusert med fenylbutazon (opptil 100 %).
Akutt giftighet av forbindelsene ble bestemt og LD 50 ved oral tilførsel varierer fra 70 til mer enn 1000 mg/kg.
Forbindelsene som har antidepressive, analgetiske og antiulcerøse egenskaper kan anvendes for behandling av depresjoner, smerter med forskjellig opphav (for eksempel postkirurgisk, dental, migrene) og gastriske, duoden-eller gastro-duoden-ulcer.
Forbindelsene kan tilføres oralt eller parenteralt, i form av farmasøytiske preparater som inneholder den aktive substans i assosiasjon med vanlige tilsetningsmidler, for eksempel i form av tabletter, dragéer, geler, kapsler eller drikkbare eller injiserbare oppløsninger eller suspensjoner.
Daglig dose utgjør 10 til 2000 mg.
Claims (1)
- Analogifremgangsmåte for fremstilling av terapeutisk aktive difenylazometinderivater med formel Ihvori X^ , , X^ og X^ uavhengig av hverandre betyr hydrogen, halogen, nitro, cyano, hydroksy, metoksy, C1 til C3~ alkyl, allyl eller fenyl, og - R representerer lH-2-imidazolyl og n er 1, eller - R representerer lH-4-imidazolyl og n er 1 eller 2, karakterisert ved at et benzofenofl (II) hvori X^ , X2 , X^ og X^ har den ovennevnte betydning, omsettes med en forbindelse (III) H„N(CH0 ) R ( <I> II ) Z Zn hvori n og R har den ovennevnte betydning, eventuelt i form av hydrokloridet.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8310974A FR2548183B1 (fr) | 1983-07-01 | 1983-07-01 | Diphenylazomethines portant un radical imidazolyle, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO842636L true NO842636L (no) | 1985-01-02 |
Family
ID=9290407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO842636A NO842636L (no) | 1983-07-01 | 1984-06-29 | Analogifremgangsmaate for fremstilling av terapeutisk aktive difenylazometinderivater |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4558062A (no) |
| EP (1) | EP0133061A1 (no) |
| JP (1) | JPS6036462A (no) |
| KR (1) | KR850001172A (no) |
| AU (1) | AU3004384A (no) |
| CA (1) | CA1220783A (no) |
| DK (1) | DK320084A (no) |
| ES (1) | ES8503337A1 (no) |
| FI (1) | FI842644A (no) |
| FR (1) | FR2548183B1 (no) |
| GR (1) | GR79541B (no) |
| HU (1) | HU192987B (no) |
| IL (1) | IL72257A0 (no) |
| NO (1) | NO842636L (no) |
| NZ (1) | NZ208719A (no) |
| PT (1) | PT78827B (no) |
| ZA (1) | ZA844999B (no) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2600648B1 (fr) * | 1986-06-27 | 1988-09-09 | Synthelabo | N-imidazolylmethyl-diphenylazomethines, leur preparation et leur application en therapeutique |
| FR2661909B1 (fr) * | 1990-05-09 | 1997-08-14 | Inst Nat Sante Rech Med | Nouveaux composes agonistes du recepteur h3 de l'histamine a usage therapeutique, compositions pharmaceutiques agissant comme agonistes dudit recepteur et procede de preparation. |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2110663B (en) * | 1981-12-04 | 1985-08-07 | Farmos Group Ltd | Imidazole derivatives |
-
1983
- 1983-07-01 FR FR8310974A patent/FR2548183B1/fr not_active Expired
-
1984
- 1984-06-18 EP EP84401254A patent/EP0133061A1/fr not_active Withdrawn
- 1984-06-27 KR KR1019840003647A patent/KR850001172A/ko not_active Application Discontinuation
- 1984-06-29 NZ NZ208719A patent/NZ208719A/en unknown
- 1984-06-29 HU HU842536A patent/HU192987B/hu unknown
- 1984-06-29 JP JP59136413A patent/JPS6036462A/ja active Pending
- 1984-06-29 FI FI842644A patent/FI842644A/fi not_active Application Discontinuation
- 1984-06-29 ZA ZA844999A patent/ZA844999B/xx unknown
- 1984-06-29 AU AU30043/84A patent/AU3004384A/en not_active Abandoned
- 1984-06-29 CA CA000457817A patent/CA1220783A/en not_active Expired
- 1984-06-29 US US06/626,298 patent/US4558062A/en not_active Expired - Fee Related
- 1984-06-29 NO NO842636A patent/NO842636L/no unknown
- 1984-06-29 IL IL72257A patent/IL72257A0/xx unknown
- 1984-06-29 DK DK320084A patent/DK320084A/da not_active Application Discontinuation
- 1984-06-29 PT PT78827A patent/PT78827B/pt unknown
- 1984-06-29 GR GR75156A patent/GR79541B/el unknown
- 1984-06-29 ES ES533830A patent/ES8503337A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2548183A1 (fr) | 1985-01-04 |
| ZA844999B (en) | 1985-02-27 |
| ES533830A0 (es) | 1985-02-16 |
| FI842644A0 (fi) | 1984-06-29 |
| US4558062A (en) | 1985-12-10 |
| PT78827B (fr) | 1986-09-10 |
| EP0133061A1 (fr) | 1985-02-13 |
| IL72257A0 (en) | 1984-12-31 |
| NZ208719A (en) | 1986-10-08 |
| AU3004384A (en) | 1985-01-03 |
| FR2548183B1 (fr) | 1985-10-31 |
| JPS6036462A (ja) | 1985-02-25 |
| PT78827A (fr) | 1984-07-01 |
| DK320084A (da) | 1985-01-02 |
| KR850001172A (ko) | 1985-03-16 |
| HUT34958A (en) | 1985-05-28 |
| ES8503337A1 (es) | 1985-02-16 |
| CA1220783A (en) | 1987-04-21 |
| FI842644A (fi) | 1985-01-02 |
| DK320084D0 (da) | 1984-06-29 |
| HU192987B (en) | 1987-08-28 |
| GR79541B (no) | 1984-10-30 |
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