NO309652B1 - 5-arylindol-derivater og deres anvendelse, samt farmasöytisk blanding - Google Patents
5-arylindol-derivater og deres anvendelse, samt farmasöytisk blanding Download PDFInfo
- Publication number
- NO309652B1 NO309652B1 NO951633A NO951633A NO309652B1 NO 309652 B1 NO309652 B1 NO 309652B1 NO 951633 A NO951633 A NO 951633A NO 951633 A NO951633 A NO 951633A NO 309652 B1 NO309652 B1 NO 309652B1
- Authority
- NO
- Norway
- Prior art keywords
- ylmethyl
- indol
- alkyl
- methylpyrrolidin
- benzimidazole
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 195
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract 3
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 24
- 208000019695 Migraine disease Diseases 0.000 claims description 19
- 206010027599 migraine Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 208000006561 Cluster Headache Diseases 0.000 claims description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
- 208000019553 vascular disease Diseases 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 206010009094 Chronic paroxysmal hemicrania Diseases 0.000 claims description 6
- 206010013654 Drug abuse Diseases 0.000 claims description 6
- 208000030814 Eating disease Diseases 0.000 claims description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 208000018912 cluster headache syndrome Diseases 0.000 claims description 6
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- 125000005843 halogen group Chemical group 0.000 claims description 4
- 150000002460 imidazoles Chemical class 0.000 claims description 4
- 210000005036 nerve Anatomy 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000000862 serotonergic effect Effects 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- RKAXEJMPFFPNPA-UHFFFAOYSA-N 1-(3-piperidin-4-yl-1h-indol-5-yl)-2,3-dihydroimidazo[4,5-b]pyridine Chemical compound C1NC2=NC=CC=C2N1C(C=C12)=CC=C1NC=C2C1CCNCC1 RKAXEJMPFFPNPA-UHFFFAOYSA-N 0.000 claims description 3
- KVKWRJDNIJTMGN-UHFFFAOYSA-N 1-(3-piperidin-4-yl-1h-indol-5-yl)benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC(C#N)=CC=C2N1C(C=C12)=CC=C1NC=C2C1CCNCC1 KVKWRJDNIJTMGN-UHFFFAOYSA-N 0.000 claims description 3
- XKENJWNGLCKOBP-UHFFFAOYSA-N 1-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indol-5-yl]benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC(C#N)=CC=C2N1C(C=C12)=CC=C1NC=C2C1=CCNCC1 XKENJWNGLCKOBP-UHFFFAOYSA-N 0.000 claims description 3
- VVYZIRCWRZBWHM-UHFFFAOYSA-N 1-[3-(1-methylpyrrolidin-3-yl)-1h-indol-5-yl]-2,3-dihydroimidazo[4,5-b]pyridine Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3C4=CC=CN=C4NC3)C=C12 VVYZIRCWRZBWHM-UHFFFAOYSA-N 0.000 claims description 3
- QTEUJQNPMLXVLL-UHFFFAOYSA-N 1-[3-(1-methylpyrrolidin-3-yl)-1h-indol-5-yl]benzimidazole-5-carbonitrile Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3C4=CC=C(C=C4N=C3)C#N)C=C12 QTEUJQNPMLXVLL-UHFFFAOYSA-N 0.000 claims description 3
- STHANXGMBJYOCX-UHFFFAOYSA-N 2-[5-(2,3-dihydroimidazo[4,5-b]pyridin-1-yl)-1h-indol-3-yl]ethanamine Chemical compound C1NC2=NC=CC=C2N1C1=CC=C2NC=C(CCN)C2=C1 STHANXGMBJYOCX-UHFFFAOYSA-N 0.000 claims description 3
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000001771 impaired effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 claims description 3
- 208000012285 hip pain Diseases 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 86
- 239000001257 hydrogen Substances 0.000 abstract description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 3
- 125000002877 alkyl aryl group Chemical group 0.000 abstract 6
- 125000003118 aryl group Chemical group 0.000 abstract 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract 5
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000005518 carboxamido group Chemical group 0.000 abstract 1
- 125000004404 heteroalkyl group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 165
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- 239000011541 reaction mixture Substances 0.000 description 70
- 238000006243 chemical reaction Methods 0.000 description 65
- 239000000243 solution Substances 0.000 description 62
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- 239000007787 solid Substances 0.000 description 57
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 52
- 239000000908 ammonium hydroxide Substances 0.000 description 52
- 239000002585 base Substances 0.000 description 51
- 239000006260 foam Substances 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 238000004587 chromatography analysis Methods 0.000 description 44
- 238000004458 analytical method Methods 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 40
- 238000007363 ring formation reaction Methods 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 36
- 238000006722 reduction reaction Methods 0.000 description 36
- 230000009467 reduction Effects 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
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- 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 30
- 235000019253 formic acid Nutrition 0.000 description 30
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- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 24
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 16
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
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- 239000002253 acid Substances 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- BBSNAHSUZJDFLE-GFCCVEGCSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC1=CNC2=CC=C(N)C=C12 BBSNAHSUZJDFLE-GFCCVEGCSA-N 0.000 description 13
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- 238000010992 reflux Methods 0.000 description 11
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 9
- 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 9
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- 102000005962 receptors Human genes 0.000 description 9
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- 150000007513 acids Chemical class 0.000 description 8
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- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 7
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 7
- 206010019233 Headaches Diseases 0.000 description 7
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- 230000002378 acidificating effect Effects 0.000 description 7
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- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 6
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- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- KEOULQHBHFWLGJ-UHFFFAOYSA-N 5-(2,5-dimethylpyrrol-1-yl)-1h-indole Chemical class CC1=CC=C(C)N1C1=CC=C(NC=C2)C2=C1 KEOULQHBHFWLGJ-UHFFFAOYSA-N 0.000 description 5
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- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 3
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 150000003852 triazoles Chemical class 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
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 210000000427 trigeminal ganglion Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
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
- C07D401/14—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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97075892A | 1992-11-02 | 1992-11-02 | |
| PCT/US1993/009790 WO1994010171A1 (en) | 1992-11-02 | 1993-10-19 | 5-arylindole derivatives and their use as serotonin (5-ht1) agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO951633D0 NO951633D0 (no) | 1995-04-28 |
| NO951633L NO951633L (no) | 1995-04-28 |
| NO309652B1 true NO309652B1 (no) | 2001-03-05 |
Family
ID=25517470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO951633A NO309652B1 (no) | 1992-11-02 | 1995-04-28 | 5-arylindol-derivater og deres anvendelse, samt farmasöytisk blanding |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US5886008A (zh) |
| EP (2) | EP1094064A1 (zh) |
| JP (1) | JP2788551B2 (zh) |
| KR (1) | KR0163371B1 (zh) |
| CN (1) | CN1051313C (zh) |
| AT (1) | ATE202102T1 (zh) |
| AU (1) | AU685066B2 (zh) |
| BR (1) | BR9307348A (zh) |
| CA (2) | CA2340999C (zh) |
| CZ (1) | CZ283001B6 (zh) |
| DE (1) | DE69330351T2 (zh) |
| DK (1) | DK0666858T3 (zh) |
| EG (1) | EG20396A (zh) |
| ES (1) | ES2157224T3 (zh) |
| FI (2) | FI111257B (zh) |
| GR (1) | GR3036579T3 (zh) |
| HU (1) | HU222235B1 (zh) |
| IL (1) | IL107386A (zh) |
| MY (1) | MY109696A (zh) |
| NO (1) | NO309652B1 (zh) |
| NZ (1) | NZ257059A (zh) |
| PL (1) | PL176091B1 (zh) |
| PT (1) | PT666858E (zh) |
| RU (1) | RU2134266C1 (zh) |
| TW (1) | TW251284B (zh) |
| WO (1) | WO1994010171A1 (zh) |
| ZA (1) | ZA938137B (zh) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9210400D0 (en) * | 1992-05-15 | 1992-07-01 | Merck Sharp & Dohme | Therapeutic agents |
| EP0716649B1 (en) * | 1993-08-31 | 1998-09-09 | Pfizer Inc. | 5-arylindole derivatives |
| US5688809A (en) * | 1994-02-10 | 1997-11-18 | Pfizer Inc. | 5-heteroarylindole derivatives |
| GB9420529D0 (en) | 1994-10-12 | 1994-11-30 | Pfizer Ltd | Indoles |
| AU702322B2 (en) * | 1995-03-20 | 1999-02-18 | Eli Lilly And Company | 5-substituted-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1h-indoles: new 5-ht1f agonists |
| US5942536A (en) * | 1995-10-10 | 1999-08-24 | Eli Lilly And Company | N- 2-substituted-3-(2-aminoethyl)-1H-indol-5-YL!-Amides: new 5-HT1F agonists |
| HUP0100179A3 (en) | 1997-07-03 | 2002-12-28 | Bristol Myers Squibb Pharma Co | Imidazopyrimidine and imidazopyridine derivatives and pharmaceutical compositions thereof |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| EP1100501A4 (en) * | 1998-06-30 | 2002-12-04 | Lilly Co Eli | PYRROLIDINE AND PYRROLIDINE DERIVATIVES INFLUENTING THE SYSTEMS ASSOCIATED WITH SEROTONIN |
| US6365589B1 (en) | 1998-07-02 | 2002-04-02 | Bristol-Myers Squibb Pharma Company | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
| US5994352A (en) * | 1998-11-13 | 1999-11-30 | Pfizer Inc. | 5-arylindole derivatives |
| PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| DE60336576D1 (de) | 2002-10-30 | 2011-05-12 | Merck Sharp & Dohme | Hemmer der akt aktivität |
| US20040102360A1 (en) * | 2002-10-30 | 2004-05-27 | Barnett Stanley F. | Combination therapy |
| US7332508B2 (en) * | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
| CA2522430A1 (en) | 2003-04-24 | 2004-11-11 | Merck & Co., Inc. | Inhibitors of akt activity |
| DE10337184A1 (de) | 2003-08-13 | 2005-03-10 | Gruenenthal Gmbh | Substituierte 3-Pyrrolidin-Indol-Derivate |
| US7442709B2 (en) * | 2003-08-21 | 2008-10-28 | Osi Pharmaceuticals, Inc. | N3-substituted imidazopyridine c-Kit inhibitors |
| EP1658289B1 (en) * | 2003-08-21 | 2009-03-18 | OSI Pharmaceuticals, Inc. | 3-substituted imidazopyridine-derivatives as c-kit inhibitors |
| CA2540541C (en) | 2003-10-03 | 2012-03-27 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
| JP4891088B2 (ja) | 2003-11-25 | 2012-03-07 | スリーエム イノベイティブ プロパティズ カンパニー | 置換されたイミダゾ環系および方法 |
| DE102004014304A1 (de) * | 2004-03-22 | 2005-10-06 | Grünenthal GmbH | Substituierte 1,4,8- Triazaspiro[4,5]decan-2-on-Verbindungen |
| AU2006210392A1 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune response modifiers |
| CA2891122C (en) | 2012-11-14 | 2021-07-20 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| AU2014228512A1 (en) | 2013-03-15 | 2015-10-01 | Agenebio, Inc. | Methods and compositions for improving cognitive function |
| US10513523B2 (en) | 2015-04-29 | 2019-12-24 | Janssen Pharmaceutica Nv | Imidazopyrazines and pyrazolopyrimidines and their use as AMPA receptor modulators |
| CA2984290C (en) | 2015-04-29 | 2022-03-01 | Janssen Pharmaceutica Nv | Benzimidazolone and benzothiazolone compounds and their use as ampa receptor modulators |
| US10604484B2 (en) | 2015-04-29 | 2020-03-31 | Janssen Pharmaceutica Nv | Indolone compounds and their use as AMPA receptor modulators |
| CN107835814B (zh) * | 2015-04-29 | 2021-07-23 | 詹森药业有限公司 | 氮杂苯并咪唑及其作为ampa受体调节剂的用途 |
| CA2986598C (en) | 2015-05-22 | 2023-09-26 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
| CN108137561B (zh) | 2015-11-06 | 2021-03-26 | 豪夫迈·罗氏有限公司 | 二氢吲哚-2-酮衍生物 |
| JP6857653B2 (ja) | 2015-11-06 | 2021-04-14 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｃｎｓ及び関連障害の治療において使用するためのインドリン−２−オン誘導体 |
| JP6857651B2 (ja) | 2015-11-06 | 2021-04-14 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｃｎｓ疾患の処置に有用なインドリン−２−オン誘導体 |
| SG11201803796SA (en) | 2015-11-06 | 2018-06-28 | Hoffmann La Roche | Indolin-2-one derivatives |
| CN111822047B (zh) * | 2020-07-17 | 2022-05-27 | 曲阜师范大学 | 一种磁性介孔聚合离子液体负载催化合成吲哚类衍生物的方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA795239B (en) * | 1978-10-12 | 1980-11-26 | Glaxo Group Ltd | Heterocyclic compounds |
| BE889931A (fr) * | 1980-08-12 | 1982-02-11 | Glaxo Group Ltd | Derives indoliques, leur preparation et leurs applications en tant que medicaments |
| US4983622A (en) * | 1984-02-06 | 1991-01-08 | Eli Lilly And Company | 6-substituted-4-dialkylaminotetrahydrobenz(c,d)indoles |
| GB8600397D0 (en) * | 1986-01-08 | 1986-02-12 | Glaxo Group Ltd | Chemical compounds |
| GB8719167D0 (en) * | 1987-08-13 | 1987-09-23 | Glaxo Group Ltd | Chemical compounds |
| GB8724912D0 (en) * | 1987-10-23 | 1987-11-25 | Wellcome Found | Indole derivatives |
| GB8819024D0 (en) * | 1988-08-10 | 1988-09-14 | Glaxo Group Ltd | Chemical compounds |
| IL96891A0 (en) * | 1990-01-17 | 1992-03-29 | Merck Sharp & Dohme | Indole-substituted five-membered heteroaromatic compounds,their preparation and pharmaceutical compositions containing them |
| US5340838A (en) * | 1990-05-04 | 1994-08-23 | Eli Lilly And Company | Method of inhibiting gastric acid secretion with 2-phenylcyclopropylamines |
| CA2042295A1 (fr) * | 1990-05-15 | 1991-11-16 | Jacques Chauveau | Derives de mediateurs endogenes, leurs sels, procede de preparation, applications, et compositions les renfermant |
| PT97888B (pt) * | 1990-06-07 | 1998-12-31 | Zeneca Ltd | Processo para a preparacao de compostos heterociclicos derivados de indol e de composicoes farmaceuticas que os contem |
| DK158590D0 (da) * | 1990-07-02 | 1990-07-02 | Lundbeck & Co As H | Indolderivater |
| HU225055B1 (en) * | 1990-10-15 | 2006-05-29 | Pfizer | Indole derivatives, their intermediates, process for production them and pharmaceutical compositions containing the compounds |
| CZ283018B6 (cs) * | 1991-02-01 | 1997-12-17 | Merck Sharp And Dohme Limited | Deriváty imidazolu, triazolu a tetrazolu a farmaceutické přípravky na jejich bázi |
| FR2672602B1 (fr) * | 1991-02-12 | 1993-06-04 | Centre Nat Rech Scient | Composes derives des beta-carbolines ligands du recepteur des benzodiazepines ayant un effet agoniste inverse et antagoniste vis-a-vis des benzodiazepines et medicaments les contenant. |
| US5229401A (en) * | 1991-09-23 | 1993-07-20 | Hoechst-Roussel Pharmaceuticals Incorporated | Substituted pyridinylamino benzo[b]thiophene compounds |
| US5187159A (en) * | 1991-10-07 | 1993-02-16 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a substituted 1,3-benzodioxole or 1,3-benzodithiole |
| GB9210400D0 (en) * | 1992-05-15 | 1992-07-01 | Merck Sharp & Dohme | Therapeutic agents |
| US5378846A (en) * | 1993-06-11 | 1995-01-03 | Russian-American Institute For New Drug Development | 1,2,3,4-tetrahydropyrrolo-[1,2-a]-pyrazine derivatives |
-
1993
- 1993-10-16 TW TW082108604A patent/TW251284B/zh active
- 1993-10-19 WO PCT/US1993/009790 patent/WO1994010171A1/en active IP Right Grant
- 1993-10-19 KR KR1019950701729A patent/KR0163371B1/ko not_active IP Right Cessation
- 1993-10-19 CA CA002340999A patent/CA2340999C/en not_active Expired - Fee Related
- 1993-10-19 NZ NZ257059A patent/NZ257059A/en unknown
- 1993-10-19 AT AT93923389T patent/ATE202102T1/de not_active IP Right Cessation
- 1993-10-19 EP EP00124422A patent/EP1094064A1/en not_active Withdrawn
- 1993-10-19 ES ES93923389T patent/ES2157224T3/es not_active Expired - Lifetime
- 1993-10-19 DE DE69330351T patent/DE69330351T2/de not_active Expired - Fee Related
- 1993-10-19 CZ CZ951108A patent/CZ283001B6/cs not_active IP Right Cessation
- 1993-10-19 PT PT93923389T patent/PT666858E/pt unknown
- 1993-10-19 DK DK93923389T patent/DK0666858T3/da active
- 1993-10-19 RU RU95109927/04A patent/RU2134266C1/ru not_active IP Right Cessation
- 1993-10-19 JP JP6511101A patent/JP2788551B2/ja not_active Expired - Lifetime
- 1993-10-19 EP EP93923389A patent/EP0666858B1/en not_active Expired - Lifetime
- 1993-10-19 US US08/424,357 patent/US5886008A/en not_active Expired - Fee Related
- 1993-10-19 AU AU53294/94A patent/AU685066B2/en not_active Ceased
- 1993-10-19 CA CA002148380A patent/CA2148380C/en not_active Expired - Fee Related
- 1993-10-19 BR BR9307348A patent/BR9307348A/pt not_active Application Discontinuation
- 1993-10-25 IL IL10738693A patent/IL107386A/en not_active IP Right Cessation
- 1993-11-01 FI FI934825A patent/FI111257B/fi not_active IP Right Cessation
- 1993-11-01 MY MYPI93002280A patent/MY109696A/en unknown
- 1993-11-01 ZA ZA938137A patent/ZA938137B/xx unknown
- 1993-11-01 CN CN93120716A patent/CN1051313C/zh not_active Expired - Fee Related
- 1993-11-02 EG EG69793A patent/EG20396A/xx active
- 1993-11-02 HU HU9303118A patent/HU222235B1/hu not_active IP Right Cessation
-
1995
- 1995-04-28 NO NO951633A patent/NO309652B1/no not_active IP Right Cessation
- 1995-05-01 PL PL93308669A patent/PL176091B1/pl unknown
-
2000
- 2000-11-15 FI FI20002505A patent/FI20002505A/fi unknown
-
2001
- 2001-09-11 GR GR20010401436T patent/GR3036579T3/el not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
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| MM1K | Lapsed by not paying the annual fees |