RU2144535C1 - Производные индола - Google Patents
Производные индола Download PDFInfo
- Publication number
- RU2144535C1 RU2144535C1 RU96108920A RU96108920A RU2144535C1 RU 2144535 C1 RU2144535 C1 RU 2144535C1 RU 96108920 A RU96108920 A RU 96108920A RU 96108920 A RU96108920 A RU 96108920A RU 2144535 C1 RU2144535 C1 RU 2144535C1
- Authority
- RU
- Russia
- Prior art keywords
- indole
- solution
- dichloro
- carboxylic acid
- phenyl
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title claims abstract description 7
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 232
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 19
- 239000000460 chlorine Substances 0.000 claims abstract description 8
- 239000005557 antagonist Substances 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 7
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 50
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 9
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 9
- 239000004471 Glycine Substances 0.000 claims description 8
- 239000003257 excitatory amino acid Substances 0.000 claims description 8
- 230000002461 excitatory amino acid Effects 0.000 claims description 8
- 150000003950 cyclic amides Chemical class 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 230000003042 antagnostic effect Effects 0.000 claims description 4
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 3
- FUCNSPFWHPFVNG-UHFFFAOYSA-N 3-[[1-(4-acetamidophenyl)-5-oxopyrazolidin-4-ylidene]methyl]-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound C1=CC(NC(=O)C)=CC=C1N(NC1)C(=O)C1=CC1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 FUCNSPFWHPFVNG-UHFFFAOYSA-N 0.000 claims description 3
- WGRGCSWDQJFFBK-UHFFFAOYSA-N 3-[[1-[4-(carbamoylamino)phenyl]-5-oxopyrazolidin-4-ylidene]methyl]-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound C1=CC(NC(=O)N)=CC=C1N(NC1)C(=O)C1=CC1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 WGRGCSWDQJFFBK-UHFFFAOYSA-N 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 34
- 238000002360 preparation method Methods 0.000 abstract description 8
- 150000001413 amino acids Chemical class 0.000 abstract description 2
- 239000013543 active substance Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 189
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 178
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 146
- 239000000543 intermediate Substances 0.000 description 121
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 98
- -1 hydroxy, methoxy, amino Chemical group 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 73
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- 238000005160 1H NMR spectroscopy Methods 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 239000002904 solvent Substances 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 35
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 23
- 239000000843 powder Substances 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 235000019270 ammonium chloride Nutrition 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 16
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 14
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 13
- 238000005299 abrasion Methods 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 125000004663 dialkyl amino group Chemical group 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000004770 neurodegeneration Effects 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 150000003333 secondary alcohols Chemical class 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 0 C*C(C1)C=CC2=C1C(*)C(C(O)=O)=C2C=C(*C)C(C*)=O Chemical compound C*C(C1)C=CC2=C1C(*)C(C(O)=O)=C2C=C(*C)C(C*)=O 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229960001681 croscarmellose sodium Drugs 0.000 description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008241 heterogeneous mixture Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
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- ZUMFRWWUBKQWJK-UHFFFAOYSA-N tert-butyl 2-(2-adamantyl)-3-oxopyrazolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)N1C1C(C2)CC3CC2CC1C3 ZUMFRWWUBKQWJK-UHFFFAOYSA-N 0.000 description 1
- MGARABDLUHQUKO-UHFFFAOYSA-N tert-butyl 2-naphthalen-1-yl-3-oxopyrazolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)N1C1=CC=CC2=CC=CC=C12 MGARABDLUHQUKO-UHFFFAOYSA-N 0.000 description 1
- IKUFSJMWDFTJFQ-UHFFFAOYSA-N tert-butyl 3-oxo-2-phenyldiazinane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)N1C1=CC=CC=C1 IKUFSJMWDFTJFQ-UHFFFAOYSA-N 0.000 description 1
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- YPSJLWUERNMQDG-UHFFFAOYSA-N tert-butyl 3-oxo-2-quinolin-2-ylpyrazolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)N1C1=CC=C(C=CC=C2)C2=N1 YPSJLWUERNMQDG-UHFFFAOYSA-N 0.000 description 1
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- GZNVLFZCNZCRQW-UHFFFAOYSA-N tert-butyl n-(3-nitroanilino)carbamate Chemical compound CC(C)(C)OC(=O)NNC1=CC=CC([N+]([O-])=O)=C1 GZNVLFZCNZCRQW-UHFFFAOYSA-N 0.000 description 1
- OKXCVETZQNAVRC-UHFFFAOYSA-N tert-butyl n-(4-aminoanilino)carbamate Chemical compound CC(C)(C)OC(=O)NNC1=CC=C(N)C=C1 OKXCVETZQNAVRC-UHFFFAOYSA-N 0.000 description 1
- DSENJXGTVKUGDS-UHFFFAOYSA-N tert-butyl n-(naphthalen-1-ylamino)carbamate Chemical compound C1=CC=C2C(NNC(=O)OC(C)(C)C)=CC=CC2=C1 DSENJXGTVKUGDS-UHFFFAOYSA-N 0.000 description 1
- UBCSHKDFGZZWMP-UHFFFAOYSA-N tert-butyl n-(quinolin-2-ylamino)carbamate Chemical compound C1=CC=CC2=NC(NNC(=O)OC(C)(C)C)=CC=C21 UBCSHKDFGZZWMP-UHFFFAOYSA-N 0.000 description 1
- MUJSUWBXFREPLD-UHFFFAOYSA-N tert-butyl n-[[3-(3-chloropropanoyl)pyridin-2-yl]amino]carbamate Chemical compound CC(C)(C)OC(=O)NNC1=NC=CC=C1C(=O)CCCl MUJSUWBXFREPLD-UHFFFAOYSA-N 0.000 description 1
- GEYCQWXDNQMORY-UHFFFAOYSA-N tert-butyl n-[[3-(3-chloropropanoyl)quinolin-2-yl]amino]carbamate Chemical compound C1=CC=C2C=C(C(=O)CCCl)C(NNC(=O)OC(C)(C)C)=NC2=C1 GEYCQWXDNQMORY-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- PYEQNXVGJRAEIG-UHFFFAOYSA-N tert-butyl n-anilinocarbamate Chemical compound CC(C)(C)OC(=O)NNC1=CC=CC=C1 PYEQNXVGJRAEIG-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939321221A GB9321221D0 (en) | 1993-10-14 | 1993-10-14 | Heterocyclic compounds |
| GB9321221.5 | 1993-10-14 | ||
| PCT/EP1994/003359 WO1995010517A1 (en) | 1993-10-14 | 1994-10-12 | Indole derivatives as nmda antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU96108920A RU96108920A (ru) | 1998-08-20 |
| RU2144535C1 true RU2144535C1 (ru) | 2000-01-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU96108920A RU2144535C1 (ru) | 1993-10-14 | 1994-10-12 | Производные индола |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US5760059A (enExample) |
| EP (1) | EP0723541A1 (enExample) |
| JP (1) | JPH09503770A (enExample) |
| CN (1) | CN1070490C (enExample) |
| AP (1) | AP574A (enExample) |
| AU (1) | AU681194B2 (enExample) |
| BG (1) | BG61839B1 (enExample) |
| CA (1) | CA2171449A1 (enExample) |
| CO (1) | CO4290355A1 (enExample) |
| CZ (1) | CZ92396A3 (enExample) |
| FI (1) | FI961628A0 (enExample) |
| GB (1) | GB9321221D0 (enExample) |
| HU (1) | HU219710B (enExample) |
| IL (1) | IL111294A (enExample) |
| IS (1) | IS4219A (enExample) |
| MY (1) | MY112411A (enExample) |
| NO (1) | NO309861B1 (enExample) |
| NZ (1) | NZ274179A (enExample) |
| OA (1) | OA10578A (enExample) |
| PE (1) | PE21995A1 (enExample) |
| PL (1) | PL179568B1 (enExample) |
| RU (1) | RU2144535C1 (enExample) |
| SG (1) | SG49013A1 (enExample) |
| SK (1) | SK44996A3 (enExample) |
| TW (1) | TW283144B (enExample) |
| WO (1) | WO1995010517A1 (enExample) |
| ZA (1) | ZA947948B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2209041C2 (ru) * | 2000-06-15 | 2003-07-27 | Новосибирский научно-исследовательский институт травматологии и ортопедии | Способ лечения церебрального вазоспазма |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| GB9704499D0 (en) * | 1997-03-05 | 1997-04-23 | Glaxo Wellcome Spa | Method of manufacture |
| GB9704498D0 (en) * | 1997-03-05 | 1997-04-23 | Glaxo Wellcome Spa | Chemical compound |
| WO2000056711A1 (en) * | 1999-03-23 | 2000-09-28 | Sumitomo Pharmaceuticals Co., Ltd. | Tricyclic indole-2-carboxylic acid compound used as nmda receptor antagonist |
| DE10153346A1 (de) | 2001-10-29 | 2004-04-22 | Grünenthal GmbH | Substituierte Indole |
| WO2003039540A2 (en) * | 2001-11-09 | 2003-05-15 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| KR20060128976A (ko) | 2003-12-29 | 2006-12-14 | 세프라코 아이엔시. | 피롤 및 피라졸 디에이에이오 억제제 |
| CA2957667A1 (en) | 2005-07-06 | 2007-01-11 | Sepracor Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
| RU2425830C2 (ru) * | 2005-12-01 | 2011-08-10 | Ф. Хоффманн-Ля Рош Аг | Новые производные винилогенных кислот |
| WO2007081857A2 (en) * | 2006-01-06 | 2007-07-19 | Sepracor Inc. | Cycloalkylamines as monoamine reuptake inhibitors |
| KR101381768B1 (ko) * | 2006-01-06 | 2014-04-07 | 선오비온 파마슈티컬스 인코포레이티드 | 테트랄론-기재 모노아민 재흡수 저해제 |
| AU2007233041B2 (en) | 2006-03-31 | 2013-05-02 | Sepracor Inc. | Preparation of chiral amides and amines |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
| EP2074092A2 (en) | 2007-01-18 | 2009-07-01 | Sepracor Inc. | Inhibitors of d-amino acid oxidase |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| CA2688493C (en) | 2007-05-31 | 2016-04-19 | Sepracor Inc. | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
| US20100120740A1 (en) * | 2008-08-07 | 2010-05-13 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| KR20110126132A (ko) * | 2009-03-10 | 2011-11-22 | 산텐 세이야꾸 가부시키가이샤 | 4,6-디클로로-1η-인돌-2-카르복실산 유도체 또는 이의 염을 유효 성분으로서 함유하는 시신경 장애의 예방 또는 치료제 |
| US20110034434A1 (en) * | 2009-08-07 | 2011-02-10 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| AU2012321345B2 (en) | 2011-10-03 | 2016-03-17 | The University Of Utah Research Foundation | Application of 5-HT6 receptor antagonists for the alleviation of cognitive deficits of down syndrome |
| DK3137658T3 (da) | 2014-04-30 | 2022-05-02 | Yufeng Jane Tseng | Anvendelse af kendte forbindelser som d-aminosyreoxidase-inhibitorer |
| KR20240042153A (ko) | 2016-09-14 | 2024-04-01 | 위펑 제인 쳉 | D-아미노산 옥시다제 (daao) 저해제로서 신규한 치환된 벤즈이미다졸 유도체 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0396124A2 (en) * | 1989-05-05 | 1990-11-07 | G.D. Searle & Co. | Compositions containing indole-2-carboxylate compounds for treatment of CNS disorders |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5256673A (en) * | 1983-11-25 | 1993-10-26 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Indole-3-yl-A-tetrahydropyridyl or piperidyl compounds |
| US4960786A (en) * | 1989-04-24 | 1990-10-02 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| DE4101686A1 (de) * | 1991-01-22 | 1992-07-23 | Merck Patent Gmbh | Indolderivate |
| US5284862A (en) * | 1991-03-18 | 1994-02-08 | Warner-Lambert Company | Derivatives of 2-carboxyindoles having pharmaceutical activity |
| US5145845A (en) * | 1991-05-14 | 1992-09-08 | Warner-Lambert Co. | Substituted 2-carboxylindoles having pharmaceutical activity |
| CA2083891A1 (en) * | 1991-12-03 | 1993-06-04 | Angus Murray Macleod | Heterocyclic compounds, compositions containing them and their use in therapy |
| GB9208492D0 (en) * | 1992-04-16 | 1992-06-03 | Glaxo Spa | Heterocyclic compounds |
| ZA936492B (en) * | 1992-09-10 | 1995-03-02 | Lilly Co Eli | Compounds useful as hypoglycemic agents and for treating Alzheimer's disease. |
| DE4333254A1 (de) * | 1993-09-30 | 1995-04-06 | Merck Patent Gmbh | Piperidine und Piperazine |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
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1993
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1994
- 1994-10-10 IS IS4219A patent/IS4219A/is unknown
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- 1994-10-12 AP APAP/P/1994/000685A patent/AP574A/en active
- 1994-10-12 PE PE1994252640A patent/PE21995A1/es not_active Application Discontinuation
- 1994-10-12 EP EP94928893A patent/EP0723541A1/en not_active Withdrawn
- 1994-10-12 WO PCT/EP1994/003359 patent/WO1995010517A1/en not_active Ceased
- 1994-10-12 JP JP7511283A patent/JPH09503770A/ja active Pending
- 1994-10-12 US US08/619,510 patent/US5760059A/en not_active Expired - Fee Related
- 1994-10-12 HU HU9600969A patent/HU219710B/hu not_active IP Right Cessation
- 1994-10-12 AU AU78133/94A patent/AU681194B2/en not_active Ceased
- 1994-10-12 RU RU96108920A patent/RU2144535C1/ru active
- 1994-10-12 NZ NZ274179A patent/NZ274179A/en unknown
- 1994-10-12 PL PL94313969A patent/PL179568B1/pl unknown
- 1994-10-12 SG SG1996005195A patent/SG49013A1/en unknown
- 1994-10-12 ZA ZA947948A patent/ZA947948B/xx unknown
- 1994-10-12 CA CA002171449A patent/CA2171449A1/en not_active Abandoned
- 1994-10-12 CN CN94193759A patent/CN1070490C/zh not_active Expired - Fee Related
- 1994-10-12 CO CO94046673A patent/CO4290355A1/es unknown
- 1994-10-12 CZ CZ96923A patent/CZ92396A3/cs unknown
- 1994-10-12 SK SK449-96A patent/SK44996A3/sk unknown
- 1994-10-13 IL IL11129494A patent/IL111294A/en not_active IP Right Cessation
- 1994-11-18 TW TW083110700A patent/TW283144B/zh active
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1996
- 1996-04-09 OA OA60812A patent/OA10578A/en unknown
- 1996-04-12 FI FI961628A patent/FI961628A0/fi unknown
- 1996-04-12 NO NO961475A patent/NO309861B1/no not_active IP Right Cessation
- 1996-04-16 BG BG100511A patent/BG61839B1/bg unknown
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1998
- 1998-05-29 US US09/086,522 patent/US5962496A/en not_active Expired - Lifetime
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1999
- 1999-08-16 US US09/374,982 patent/US6100289A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0396124A2 (en) * | 1989-05-05 | 1990-11-07 | G.D. Searle & Co. | Compositions containing indole-2-carboxylate compounds for treatment of CNS disorders |
Non-Patent Citations (1)
| Title |
|---|
| Машковский М.Д. Лекарственные средства. - М.: Медицина, 1972, ч.1, с.63 - 68, 112, 119. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2209041C2 (ru) * | 2000-06-15 | 2003-07-27 | Новосибирский научно-исследовательский институт травматологии и ортопедии | Способ лечения церебрального вазоспазма |
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