NO309861B1 - Indol-derivater, anvendelse derav og farmasøytisk preparat - Google Patents
Indol-derivater, anvendelse derav og farmasøytisk preparat Download PDFInfo
- Publication number
- NO309861B1 NO309861B1 NO961475A NO961475A NO309861B1 NO 309861 B1 NO309861 B1 NO 309861B1 NO 961475 A NO961475 A NO 961475A NO 961475 A NO961475 A NO 961475A NO 309861 B1 NO309861 B1 NO 309861B1
- Authority
- NO
- Norway
- Prior art keywords
- solution
- indole
- carboxylic acid
- dichloro
- ylidenemethyl
- Prior art date
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- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 4
- 150000002475 indoles Chemical class 0.000 title description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 193
- -1 2-quinolinyl Chemical group 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 32
- 150000002148 esters Chemical class 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 5
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 230000002461 excitatory amino acid Effects 0.000 claims description 4
- 239000003257 excitatory amino acid Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 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
- 230000003042 antagnostic effect Effects 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 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 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 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 2
- 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 2
- CBKAXPSTORRGPV-UHFFFAOYSA-N 4,6-dichloro-3-[(3-oxo-2-phenyl-1,2-oxazolidin-4-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C=C(C1=O)CON1C1=CC=CC=C1 CBKAXPSTORRGPV-UHFFFAOYSA-N 0.000 claims description 2
- XJELZLGPIDHDLI-UXBLZVDNSA-N 4,6-dichloro-3-[(e)-(2,5-dioxo-1-phenylpyrrolidin-3-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CC(=O)N1C1=CC=CC=C1 XJELZLGPIDHDLI-UXBLZVDNSA-N 0.000 claims description 2
- XLQOULKRIADZTN-FMIVXFBMSA-N 4,6-dichloro-3-[(e)-(2-oxo-1-phenylpiperidin-3-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CCCN1C1=CC=CC=C1 XLQOULKRIADZTN-FMIVXFBMSA-N 0.000 claims description 2
- VDIRQCDDCGAGET-DHZHZOJOSA-N 4,6-dichloro-3-[(e)-(2-oxo-1-phenylpyrrolidin-3-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical group OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CCN1C1=CC=CC=C1 VDIRQCDDCGAGET-DHZHZOJOSA-N 0.000 claims description 2
- GSPWLRZFONDXAW-UXBLZVDNSA-N 4,6-dichloro-3-[(e)-(5-oxo-1-phenylpyrazolidin-4-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical group OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CNN1C1=CC=CC=C1 GSPWLRZFONDXAW-UXBLZVDNSA-N 0.000 claims description 2
- 101150047265 COR2 gene Proteins 0.000 claims description 2
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 2
- 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 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- ZARBLYLWDMUUQC-RIYZIHGNSA-N 4,6-dichloro-3-[(e)-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)\NC(=O)N1C1=CC=CC=C1 ZARBLYLWDMUUQC-RIYZIHGNSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 189
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 174
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 148
- 239000000543 intermediate Substances 0.000 description 111
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 104
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 74
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 238000005160 1H NMR spectroscopy Methods 0.000 description 48
- 239000007787 solid Substances 0.000 description 43
- 239000002904 solvent Substances 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 23
- 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 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- 239000003480 eluent Substances 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- 238000001665 trituration Methods 0.000 description 16
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 15
- 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 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 235000019270 ammonium chloride Nutrition 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000006260 foam Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 239000000843 powder Substances 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- 239000013067 intermediate product Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
- 239000012044 organic layer Substances 0.000 description 8
- 238000010992 reflux Methods 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
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000011734 sodium Substances 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
- 239000004471 Glycine Substances 0.000 description 6
- 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 6
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 150000003950 cyclic amides Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000004770 neurodegeneration Effects 0.000 description 5
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[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
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241000699670 Mus sp. Species 0.000 description 4
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
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- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
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- 125000005041 acyloxyalkyl group Chemical group 0.000 description 3
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- 239000000010 aprotic solvent Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 3
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- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
- 231100000189 neurotoxic Toxicity 0.000 description 3
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 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
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- 238000004809 thin layer chromatography Methods 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
- 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
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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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939321221A GB9321221D0 (en) | 1993-10-14 | 1993-10-14 | Heterocyclic compounds |
| PCT/EP1994/003359 WO1995010517A1 (fr) | 1993-10-14 | 1994-10-12 | Derives d'indole utilises en tant qu'antagonistes de n-methyl-d-aspartate (nmda) |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO961475L NO961475L (no) | 1996-04-12 |
| NO961475D0 NO961475D0 (no) | 1996-04-12 |
| NO309861B1 true NO309861B1 (no) | 2001-04-09 |
Family
ID=10743550
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO961475A NO309861B1 (no) | 1993-10-14 | 1996-04-12 | Indol-derivater, anvendelse derav og farmasøytisk preparat |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US5760059A (fr) |
| EP (1) | EP0723541A1 (fr) |
| JP (1) | JPH09503770A (fr) |
| CN (1) | CN1070490C (fr) |
| AP (1) | AP574A (fr) |
| AU (1) | AU681194B2 (fr) |
| BG (1) | BG61839B1 (fr) |
| CA (1) | CA2171449A1 (fr) |
| CO (1) | CO4290355A1 (fr) |
| CZ (1) | CZ92396A3 (fr) |
| FI (1) | FI961628A (fr) |
| GB (1) | GB9321221D0 (fr) |
| HU (1) | HU219710B (fr) |
| IL (1) | IL111294A (fr) |
| IS (1) | IS4219A (fr) |
| MY (1) | MY112411A (fr) |
| NO (1) | NO309861B1 (fr) |
| NZ (1) | NZ274179A (fr) |
| OA (1) | OA10578A (fr) |
| PE (1) | PE21995A1 (fr) |
| PL (1) | PL179568B1 (fr) |
| RU (1) | RU2144535C1 (fr) |
| SG (1) | SG49013A1 (fr) |
| SK (1) | SK44996A3 (fr) |
| TW (1) | TW283144B (fr) |
| WO (1) | WO1995010517A1 (fr) |
| ZA (1) | ZA947948B (fr) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| GB9704498D0 (en) * | 1997-03-05 | 1997-04-23 | Glaxo Wellcome Spa | Chemical compound |
| GB9704499D0 (en) * | 1997-03-05 | 1997-04-23 | Glaxo Wellcome Spa | Method of manufacture |
| WO2000056711A1 (fr) * | 1999-03-23 | 2000-09-28 | Sumitomo Pharmaceuticals Co., Ltd. | Compose d'acide indole-2-carboxylique tricyclique utilise comme antagoniste du recepteur nmda |
| DE10153346A1 (de) | 2001-10-29 | 2004-04-22 | Grünenthal GmbH | Substituierte Indole |
| US20030162825A1 (en) * | 2001-11-09 | 2003-08-28 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| JP2007517056A (ja) | 2003-12-29 | 2007-06-28 | セプラコア インコーポレーテッド | ピロール及びピラゾールｄａａｏ阻害剤 |
| JP2009500425A (ja) | 2005-07-06 | 2009-01-08 | セプラコア インコーポレーテッド | エスゾピクロン及びトランス４−（３，４−ジクロロフェニル）−１，２，３，４−テトラヒドロ−ｎ−メチル−１−ナフタレンアミン又はトランス４−（３，４−ジクロロフェニル）−１，２，３，４−テトラヒドロ−１−ナフタレンアミンの組み合わせ、並びに閉経期並びに気分、不安、及び認知障害の治療方法 |
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| RU2430913C2 (ru) * | 2006-01-06 | 2011-10-10 | Сепракор Инк. | Циклоалкиламины в качестве ингибиторов повторного поглощения моноамина |
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| EP2074092A2 (fr) * | 2007-01-18 | 2009-07-01 | Sepracor Inc. | Inhibiteurs de la d-amino acide oxydase |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
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| JP2010235597A (ja) * | 2009-03-10 | 2010-10-21 | Santen Pharmaceut Co Ltd | ４，６−ジクロロ−１ｈ−インドール−２−カルボン酸誘導体又はその塩を有効成分として含有する視神経障害の予防又は治療剤 |
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| EP2763676B1 (fr) | 2011-10-03 | 2019-12-25 | The University of Utah Research Foundation | Application d'antagonistes du récepteur 5-ht6 dans l'atténuation des déficits cognitifs liés au syndrome de down |
| US9868975B2 (en) | 2014-04-30 | 2018-01-16 | Yufeng Jane Tseng | Use of known compounds as D-amino acid oxidase inhibitors |
| CA3036250C (fr) | 2016-09-14 | 2023-09-26 | Yufeng Jane Tseng | Nouveaux derives de benzimidazole substitues utilises en tant qu'inhibiteurs de la d-amino-acide oxydase (daao) |
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| 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 |
| EP0545478A1 (fr) * | 1991-12-03 | 1993-06-09 | MERCK SHARP & DOHME LTD. | Composés hétérocycliques comme tachykinine antagonistes |
| GB9208492D0 (en) * | 1992-04-16 | 1992-06-03 | Glaxo Spa | Heterocyclic compounds |
| EP0915090A1 (fr) * | 1992-09-10 | 1999-05-12 | Eli Lilly And Company | Thiazolidinones comme agents hypoglycemiants et pour le traitement de la maladie d'Alzheimer |
| 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 |
-
1993
- 1993-10-14 GB GB939321221A patent/GB9321221D0/en active Pending
-
1994
- 1994-10-10 IS IS4219A patent/IS4219A/is unknown
- 1994-10-11 MY MYPI94002695A patent/MY112411A/en unknown
- 1994-10-12 ZA ZA947948A patent/ZA947948B/xx unknown
- 1994-10-12 WO PCT/EP1994/003359 patent/WO1995010517A1/fr not_active Application Discontinuation
- 1994-10-12 EP EP94928893A patent/EP0723541A1/fr not_active Withdrawn
- 1994-10-12 CO CO94046673A patent/CO4290355A1/es unknown
- 1994-10-12 RU RU96108920A patent/RU2144535C1/ru active
- 1994-10-12 PE PE1994252640A patent/PE21995A1/es not_active Application Discontinuation
- 1994-10-12 AU AU78133/94A patent/AU681194B2/en not_active Ceased
- 1994-10-12 AP APAP/P/1994/000685A patent/AP574A/en active
- 1994-10-12 PL PL94313969A patent/PL179568B1/pl unknown
- 1994-10-12 CA CA002171449A patent/CA2171449A1/fr not_active Abandoned
- 1994-10-12 US US08/619,510 patent/US5760059A/en not_active Expired - Fee Related
- 1994-10-12 SG SG1996005195A patent/SG49013A1/en unknown
- 1994-10-12 CN CN94193759A patent/CN1070490C/zh not_active Expired - Fee Related
- 1994-10-12 JP JP7511283A patent/JPH09503770A/ja active Pending
- 1994-10-12 CZ CZ96923A patent/CZ92396A3/cs unknown
- 1994-10-12 NZ NZ274179A patent/NZ274179A/en unknown
- 1994-10-12 SK SK449-96A patent/SK44996A3/sk unknown
- 1994-10-12 HU HU9600969A patent/HU219710B/hu not_active IP Right Cessation
- 1994-10-13 IL IL11129494A patent/IL111294A/en not_active IP Right Cessation
- 1994-11-18 TW TW083110700A patent/TW283144B/zh active
-
1996
- 1996-04-09 OA OA60812A patent/OA10578A/en unknown
- 1996-04-12 NO NO961475A patent/NO309861B1/no not_active IP Right Cessation
- 1996-04-12 FI FI961628A patent/FI961628A/fi unknown
- 1996-04-16 BG BG100511A patent/BG61839B1/bg unknown
-
1998
- 1998-05-29 US US09/086,522 patent/US5962496A/en not_active Expired - Lifetime
-
1999
- 1999-08-16 US US09/374,982 patent/US6100289A/en not_active Expired - Lifetime
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