SK280173B6 - 1,5-benzodiazepínové deriváty, spôsob ich výroby, - Google Patents
1,5-benzodiazepínové deriváty, spôsob ich výroby, Download PDFInfo
- Publication number
- SK280173B6 SK280173B6 SK864-94A SK86494A SK280173B6 SK 280173 B6 SK280173 B6 SK 280173B6 SK 86494 A SK86494 A SK 86494A SK 280173 B6 SK280173 B6 SK 280173B6
- Authority
- SK
- Slovakia
- Prior art keywords
- phenyl
- solution
- give
- tetrahydro
- dioxo
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 22
- ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical class N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 11
- 239000000203 mixture Substances 0.000 title description 115
- 150000001875 compounds Chemical class 0.000 claims abstract description 276
- -1 hydroxy, phenyl Chemical group 0.000 claims abstract description 97
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 18
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 10
- 239000000460 chlorine Chemical group 0.000 claims description 10
- 102100021022 Gastrin Human genes 0.000 claims description 9
- 108010052343 Gastrins Proteins 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Chemical group 0.000 claims description 9
- 239000004202 carbamide Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
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- 230000008569 process Effects 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 230000008901 benefit Effects 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- RZERRLOTRSJIAW-UHFFFAOYSA-N 1-[1-(1-adamantylmethyl)-2,4-dioxo-5-phenyl-1,5-benzodiazepin-3-yl]-3-phenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC(C1=O)C(=O)N(CC23CC4CC(CC(C4)C2)C3)C2=CC=CC=C2N1C1=CC=CC=C1 RZERRLOTRSJIAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 239000012948 isocyanate Substances 0.000 claims description 3
- 150000002513 isocyanates Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 108010089448 Cholecystokinin B Receptor Proteins 0.000 abstract description 7
- 102100036016 Gastrin/cholecystokinin type B receptor Human genes 0.000 abstract description 5
- 239000005557 antagonist Substances 0.000 abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 4
- 102000052874 Gastrin receptors Human genes 0.000 abstract description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 285
- 239000000243 solution Substances 0.000 description 265
- 239000000543 intermediate Substances 0.000 description 217
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 183
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 149
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 130
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 104
- 239000007787 solid Substances 0.000 description 99
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 96
- 238000003818 flash chromatography Methods 0.000 description 87
- 239000012267 brine Substances 0.000 description 85
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 85
- 239000012299 nitrogen atmosphere Substances 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 70
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000003921 oil Substances 0.000 description 57
- 235000019198 oils Nutrition 0.000 description 57
- 238000005160 1H NMR spectroscopy Methods 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 239000006260 foam Substances 0.000 description 47
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- 229960000583 acetic acid Drugs 0.000 description 39
- 235000019441 ethanol Nutrition 0.000 description 35
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- 239000000284 extract Substances 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 31
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 239000012362 glacial acetic acid Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000002244 precipitate Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- DVARZUUKZACNGW-UHFFFAOYSA-N 2-(phenylhydrazinylidene)propanedioyl dichloride Chemical compound ClC(=O)C(C(Cl)=O)=NNC1=CC=CC=C1 DVARZUUKZACNGW-UHFFFAOYSA-N 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- 150000003141 primary amines Chemical class 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 13
- 229910052763 palladium Inorganic materials 0.000 description 13
- 239000011701 zinc Substances 0.000 description 13
- 229910052725 zinc Inorganic materials 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 229940049706 benzodiazepine Drugs 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- AEMWUHCKKDPRSK-UHFFFAOYSA-N (ne)-n-diazo-2,4,6-tri(propan-2-yl)benzenesulfonamide Chemical compound CC(C)C1=CC(C(C)C)=C(S(=O)(=O)N=[N+]=[N-])C(C(C)C)=C1 AEMWUHCKKDPRSK-UHFFFAOYSA-N 0.000 description 9
- 101800001982 Cholecystokinin Proteins 0.000 description 9
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
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- 239000012279 sodium borohydride Substances 0.000 description 9
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- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
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- 238000003756 stirring Methods 0.000 description 8
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 7
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 7
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- 229940087562 sodium acetate trihydrate Drugs 0.000 description 7
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 7
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- OYGRPIXAYJLZEN-UHFFFAOYSA-N 2-n-(2-fluorophenyl)benzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1F OYGRPIXAYJLZEN-UHFFFAOYSA-N 0.000 description 3
- VGOAJCYZNWXKGR-UHFFFAOYSA-N 3-amino-1-(3-methylbutyl)-5-phenyl-1,5-benzodiazepine-2,4-dione Chemical compound O=C1C(N)C(=O)N(CCC(C)C)C2=CC=CC=C2N1C1=CC=CC=C1 VGOAJCYZNWXKGR-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- 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
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929201180A GB9201180D0 (en) | 1992-01-21 | 1992-01-21 | Chemical compounds |
| PCT/EP1993/000098 WO1993014074A1 (en) | 1992-01-21 | 1993-01-19 | 1,5-benzodiazepine derivatives and their use in medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK86494A3 SK86494A3 (en) | 1995-03-08 |
| SK280173B6 true SK280173B6 (sk) | 1999-09-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK864-94A SK280173B6 (sk) | 1992-01-21 | 1993-01-19 | 1,5-benzodiazepínové deriváty, spôsob ich výroby, |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US5580895A (bg) |
| JP (1) | JP3253723B2 (bg) |
| KR (1) | KR100263625B1 (bg) |
| CN (1) | CN1049217C (bg) |
| AP (1) | AP369A (bg) |
| AU (2) | AU3450193A (bg) |
| BG (1) | BG61876B1 (bg) |
| CA (1) | CA2087672C (bg) |
| CZ (1) | CZ283950B6 (bg) |
| FI (1) | FI111632B (bg) |
| GB (1) | GB9201180D0 (bg) |
| GE (1) | GEP20001968B (bg) |
| HU (2) | HU221297B1 (bg) |
| IL (1) | IL104447A (bg) |
| IS (1) | IS3970A (bg) |
| MX (1) | MX9300261A (bg) |
| MY (1) | MY131307A (bg) |
| NO (1) | NO305952B1 (bg) |
| NZ (1) | NZ245715A (bg) |
| OA (1) | OA09964A (bg) |
| PH (1) | PH30894A (bg) |
| PL (1) | PL175340B1 (bg) |
| RO (1) | RO114128B1 (bg) |
| RU (1) | RU2124009C1 (bg) |
| SK (1) | SK280173B6 (bg) |
| TW (1) | TW226013B (bg) |
| UA (1) | UA29416C2 (bg) |
| WO (1) | WO1993014074A1 (bg) |
| ZA (1) | ZA93375B (bg) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9225492D0 (en) * | 1992-12-05 | 1993-01-27 | Glaxo Group Ltd | Amine derivatives |
| GB9307833D0 (en) * | 1993-04-15 | 1993-06-02 | Glaxo Inc | Modulators of cholecystokinin and gastrin |
| PL311083A1 (en) * | 1993-04-15 | 1996-02-05 | Glaxo Wellcome Inc | Derivatives of 1,5-bezodiazepine exhibiting antagonistic activity of cck and/or gastrin |
| GB9308421D0 (en) * | 1993-04-23 | 1993-06-09 | Glaxo Spa | Chemical compounds |
| GB9308431D0 (en) * | 1993-04-23 | 1993-06-09 | Glaxo Spa | Chemical compounds |
| GB9314977D0 (en) * | 1993-07-20 | 1993-09-01 | Glaxo Spa | Chemical compounds |
| GB2280182A (en) * | 1993-07-20 | 1995-01-25 | Glaxo Spa | Benzodiazepine derivatives |
| GB9314981D0 (en) * | 1993-07-20 | 1993-09-01 | Glaxo Spa | Chemical compounds |
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Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2641280B1 (fr) * | 1988-12-29 | 1994-01-21 | Roussel Uclaf | Nouveaux derives de la 2,4-dioxo 2,3,4,5-tetrahydro 1h-1,5-benzodiazepine, leur procede de preparation et leur application comme medicaments |
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1992
- 1992-01-21 GE GEAP19922651A patent/GEP20001968B/en unknown
- 1992-01-21 GB GB929201180A patent/GB9201180D0/en active Pending
-
1993
- 1993-01-15 US US08/256,359 patent/US5580895A/en not_active Expired - Fee Related
- 1993-01-19 PL PL93304684A patent/PL175340B1/pl unknown
- 1993-01-19 CZ CZ941736A patent/CZ283950B6/cs not_active IP Right Cessation
- 1993-01-19 RO RO94-01216A patent/RO114128B1/ro unknown
- 1993-01-19 SK SK864-94A patent/SK280173B6/sk unknown
- 1993-01-19 UA UA94005364A patent/UA29416C2/uk unknown
- 1993-01-19 AU AU34501/93A patent/AU3450193A/en not_active Abandoned
- 1993-01-19 WO PCT/EP1993/000098 patent/WO1993014074A1/en active IP Right Grant
- 1993-01-19 HU HU9402150A patent/HU221297B1/hu not_active IP Right Cessation
- 1993-01-19 KR KR1019940702491A patent/KR100263625B1/ko not_active IP Right Cessation
- 1993-01-19 RU RU94037768A patent/RU2124009C1/ru active
- 1993-01-20 MY MYPI93000093A patent/MY131307A/en unknown
- 1993-01-20 JP JP02483193A patent/JP3253723B2/ja not_active Expired - Fee Related
- 1993-01-20 IS IS3970A patent/IS3970A/is unknown
- 1993-01-20 AU AU31935/93A patent/AU661749B2/en not_active Ceased
- 1993-01-20 IL IL104447A patent/IL104447A/en not_active IP Right Cessation
- 1993-01-20 CA CA002087672A patent/CA2087672C/en not_active Expired - Fee Related
- 1993-01-20 NZ NZ245715A patent/NZ245715A/en unknown
- 1993-01-20 ZA ZA93375A patent/ZA93375B/xx unknown
- 1993-01-20 AP APAP/P/1993/000478A patent/AP369A/en active
- 1993-01-20 PH PH45583A patent/PH30894A/en unknown
- 1993-01-20 MX MX9300261A patent/MX9300261A/es not_active IP Right Cessation
- 1993-01-21 CN CN93101143A patent/CN1049217C/zh not_active Expired - Fee Related
- 1993-02-02 TW TW082100666A patent/TW226013B/zh active
-
1994
- 1994-06-27 BG BG98881A patent/BG61876B1/bg unknown
- 1994-07-18 OA OA60539A patent/OA09964A/en unknown
- 1994-07-19 FI FI943421A patent/FI111632B/fi active
- 1994-07-20 NO NO942720A patent/NO305952B1/no unknown
-
1995
- 1995-06-16 HU HU95P/P00242P patent/HU211295A9/hu unknown
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1996
- 1996-07-01 US US08/674,259 patent/US5637697A/en not_active Expired - Fee Related
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