CA2284218A1 - Derives d'isoquinoline substituee et leur utilisation en tant qu'anticonvulsivants - Google Patents
Derives d'isoquinoline substituee et leur utilisation en tant qu'anticonvulsivants Download PDFInfo
- Publication number
- CA2284218A1 CA2284218A1 CA002284218A CA2284218A CA2284218A1 CA 2284218 A1 CA2284218 A1 CA 2284218A1 CA 002284218 A CA002284218 A CA 002284218A CA 2284218 A CA2284218 A CA 2284218A CA 2284218 A1 CA2284218 A1 CA 2284218A1
- Authority
- CA
- Canada
- Prior art keywords
- tetrahydroisoquinolin
- methyl
- bromo
- iso
- methoxybenzamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000001961 anticonvulsive agent Substances 0.000 title claims description 11
- 229940125681 anticonvulsant agent Drugs 0.000 title description 3
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 149
- -1 trifluoromethyldiazirinyl Chemical group 0.000 claims abstract description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 58
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 206010015037 epilepsy Diseases 0.000 claims abstract description 10
- 238000011321 prophylaxis Methods 0.000 claims abstract description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 4
- NIQACKZWCXEBSV-UHFFFAOYSA-N 4-tert-butyl-n-(8-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-5-yl)-2-methoxybenzamide Chemical compound COC1=CC(C(C)(C)C)=CC=C1C(=O)NC1=CC=C(F)C2=C1CCN(C)C2 NIQACKZWCXEBSV-UHFFFAOYSA-N 0.000 claims abstract description 4
- VLJGTIAWOFBIRR-UHFFFAOYSA-N 5-benzoyl-n-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-methoxybenzamide Chemical compound C1=C(C(=O)NC=2C=C3CNCCC3=C(I)C=2)C(OC)=CC=C1C(=O)C1=CC=CC=C1 VLJGTIAWOFBIRR-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
- PMRSETIJSQHJTO-UHFFFAOYSA-N 5-benzoyl-n-(7-iodo-2-methyl-3,4-dihydro-1h-isoquinolin-5-yl)-2-methoxybenzamide Chemical compound C1=C(C(=O)NC=2C=3CCN(C)CC=3C=C(I)C=2)C(OC)=CC=C1C(=O)C1=CC=CC=C1 PMRSETIJSQHJTO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- DEOBZMPAXSKSDG-UHFFFAOYSA-N n-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-(1-methoxydiazirin-3-yl)-4-(trifluoromethyl)benzamide Chemical compound CON1N=C1C1=CC(C(F)(F)F)=CC=C1C(=O)NC1=CC(I)=C(CCNC2)C2=C1 DEOBZMPAXSKSDG-UHFFFAOYSA-N 0.000 claims abstract description 3
- IVYRYKVNZGPSJP-UHFFFAOYSA-N n-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-(1-methoxydiazirin-3-yl)-5-(trifluoromethyl)benzamide Chemical compound CON1N=C1C1=CC=C(C(F)(F)F)C=C1C(=O)NC1=CC(I)=C(CCNC2)C2=C1 IVYRYKVNZGPSJP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 2
- LRBSCNASLDWCOR-UHFFFAOYSA-N 5-benzoyl-n-(7-iodo-1,2,3,4-tetrahydroisoquinolin-5-yl)-2-methoxybenzamide Chemical compound C1=C(C(=O)NC=2C=3CCNCC=3C=C(I)C=2)C(OC)=CC=C1C(=O)C1=CC=CC=C1 LRBSCNASLDWCOR-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 52
- 238000002360 preparation method Methods 0.000 claims description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
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- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 11
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- 239000012453 solvate Substances 0.000 claims description 9
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
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- 206010008748 Chorea Diseases 0.000 claims description 8
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- 206010026749 Mania Diseases 0.000 claims description 8
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- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 8
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- 229940049706 benzodiazepine Drugs 0.000 claims description 8
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 8
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- 208000021722 neuropathic pain Diseases 0.000 claims description 8
- 229960002715 nicotine Drugs 0.000 claims description 8
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 8
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- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 8
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- 206010003591 Ataxia Diseases 0.000 claims description 6
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- YRUAGXGJJDJVQP-UHFFFAOYSA-N 3-bromo-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)-4-propan-2-ylbenzamide Chemical compound C1=C(Br)C(C(C)C)=CC=C1C(=O)NC1=CC=C(CCN(C)C2)C2=C1 YRUAGXGJJDJVQP-UHFFFAOYSA-N 0.000 claims description 3
- JCMGCQYTXXDTIA-UHFFFAOYSA-N 2,4-dichloro-5-fluoro-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C1=CC(F)=C(Cl)C=C1Cl JCMGCQYTXXDTIA-UHFFFAOYSA-N 0.000 claims description 2
- IZTGCMASDIMYQY-UHFFFAOYSA-N 2-methyl-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)-1,3-thiazole-4-carboxamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C1=CSC(C)=N1 IZTGCMASDIMYQY-UHFFFAOYSA-N 0.000 claims description 2
- HSXULVSXQLODTJ-UHFFFAOYSA-N 3-bromo-4-ethyl-n-[1-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]benzamide Chemical compound C1=C(Br)C(CC)=CC=C1C(=O)NC1=CC=C(CCNC2CCO)C2=C1 HSXULVSXQLODTJ-UHFFFAOYSA-N 0.000 claims description 2
- SVFLVFCOGYPJRC-UHFFFAOYSA-N 3-bromo-n-(5-chloro-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)-4-ethylbenzamide Chemical compound C1=C(Br)C(CC)=CC=C1C(=O)NC1=CC(Cl)=C(CCN(C)C2)C2=C1 SVFLVFCOGYPJRC-UHFFFAOYSA-N 0.000 claims description 2
- LBCLBFPXYHPIJA-UHFFFAOYSA-N 3-chloro-N-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-4-propan-2-yloxybenzamide 2-methyl-N-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-3H-benzimidazole-5-carboxamide Chemical compound CN1CCc2ccc(NC(=O)c3ccc4[nH]c(C)nc4c3)cc2C1.CC(C)Oc1ccc(cc1Cl)C(=O)Nc1ccc2CCN(C)Cc2c1 LBCLBFPXYHPIJA-UHFFFAOYSA-N 0.000 claims description 2
- UDGBFMXGUNSWAZ-UHFFFAOYSA-N 3-cyano-N-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-4-propoxybenzamide 3-fluoro-4-methoxy-N-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)benzamide hydrochloride Chemical compound CN1CC2=CC(=CC=C2CC1)NC(C1=CC(=C(C=C1)OCCC)C#N)=O.CN1CC2=CC(=CC=C2CC1)NC(C1=CC(=C(C=C1)OC)F)=O.Cl UDGBFMXGUNSWAZ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 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
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 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 1
- AGRBXKCSGCUXST-UHFFFAOYSA-N tert-butyl 7-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C(N)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AGRBXKCSGCUXST-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical class OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
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- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- 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
- A61P25/08—Antiepileptics; Anticonvulsants
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Plural Heterocyclic Compounds (AREA)
Abstract
Composés de la formule (I) et sels pharmaceutiquement acceptables de ces composés. Dans cette formule, Q représente un aryle monocyclique ou bicyclique ou un noyau hétéroaryle; R?1¿ représente de l'hydrogène, un C¿1-6?alkyle (éventuellement substitué par un hydroxy ou un C¿1-4?alkoxy), un C¿1-6?alcényle, un C¿1-6?alkynyle, un C¿1-6?alkylCO-, un formyle, un CF¿3?CO- ou un C¿1-6?alkylSO¿2?-, R?2¿ représente de l'hydrogène ou jusqu'à trois substituants sélectionnés à partir d'un halogène, de NO¿2?, CN, N¿3?, CF¿3?O-, CF¿3?S-, CF¿3?CO-, de trifluorométhyldiazirinyle, C¿1-6?alkyle, C¿1-6?alcényle, C¿1-6?alkynyle, C¿1-6?perfluoroalkyle, C¿3-6?cycloalkyle, C¿3-6?cycloalkyl-C¿1-4?alkyl-, C¿1-6?alkylO-, C¿1-6?alkylCO-, C¿3-6?cycloalkylO-, C¿3-6?cycloalkylCO-, C¿3-6?cycloalkyl-C¿1-4?alkylO-, C¿3-6?cycloalkyl-C¿1-4?alkylCO-, phényle, phénoxy, benzyloxy, benzoyle, phényl-C¿1-4?alkyl-, C¿1-6?alkylS-, C¿1-6?alkylSO¿2?-, (C¿1-4?alkyl)¿2?NSO¿2-?, (C¿1-4?alkyl)NHSO¿2?-, (C¿1-4?alkyl)¿2?NCO-, (C¿1-4?alkyl)NHCO- ou CONH¿2?; ou bien -NR?3¿R?4¿ où R?3¿ représente de l'hydrogène ou C¿1-4?alkyl et R?4¿ représente de l'hydrogène, C¿1-4?alkyle, formyle, -CO¿2?C¿1-4?alkyle ou -COC¿1-4?alkyle; ou bien deux groupes R?2¿ forment ensemble un noyau carbocyclique qui est saturé ou non et substitué ou non par -OH ou =OH; et X représente de l'hydrogène, halogène, C¿1-6?alkoxy, C¿1-6?alkyle, amino ou trifluoroacétylamino; mais lorsque X représente de l'hydrogène, cela exclue les composés dans lesquels R?2¿ représente 2-alkoxy et lorsque X représente de l'halogène, cela exclue les composés N-(7-iodo-2-méthyl-1,2,3,4-tétrahydroisoquinolin-5-yl) -5-benzoyl-2-méthoxybenzamide, N-(7-iodo-1,2,3,4-tétrahydroisoquinolin-5-yl) -5-benzoyl-2-méthoxybenzamide, N-(5-iodo-1,2,3,4-tétrahydroisoquinolin-7-yl) -5-benzoyl-2-méthoxybenzamide, N-(5-iodo-1,2,3,4-tétrahydroisoquinolin-7-yl) -2-méthoxy-4-trifluorométhyldiazirinylbenzamide, N-(5-iodo-1,2,3,4-tétrahydroisoquinolin-7-yl) -2-méthoxy-5-trifluorométhyldiazirinylbenzamide, N-(7-iodo-1,2,3,4,-tétrahydroisoquinolin-5-yl) -2-méthoxy-5-trifluorométhyldiazirinylbenzamide et N-(8-fluoro-2-méthyl-1,2,3,4-tétrahydroisoquinolin-5-yl) -4-t-butyl-2-méthoxybenzamide. Ces composés sont utilisés, entre autres choses, dans le traitement et la prophylaxie de l'épilepsie.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9705619.6A GB9705619D0 (en) | 1997-03-18 | 1997-03-18 | Novel compounds |
| GB9705619.6 | 1997-03-18 | ||
| GBGB9726695.1A GB9726695D0 (en) | 1997-12-17 | 1997-12-17 | Novel compounds |
| GB9726695.1 | 1997-12-17 | ||
| PCT/GB1998/000782 WO1998041508A1 (fr) | 1997-03-18 | 1998-03-16 | Derives d'isoquinoline substituee et leur utilisation en tant qu'anticonvulsivants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2284218A1 true CA2284218A1 (fr) | 1998-09-24 |
Family
ID=26311215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002284218A Abandoned CA2284218A1 (fr) | 1997-03-18 | 1998-03-16 | Derives d'isoquinoline substituee et leur utilisation en tant qu'anticonvulsivants |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0968190A1 (fr) |
| JP (1) | JP3690423B2 (fr) |
| KR (1) | KR100568654B1 (fr) |
| CN (1) | CN1183116C (fr) |
| AR (1) | AR012092A1 (fr) |
| AU (1) | AU737955B2 (fr) |
| BR (1) | BR9809047A (fr) |
| CA (1) | CA2284218A1 (fr) |
| CO (1) | CO4950553A1 (fr) |
| IL (1) | IL131756A0 (fr) |
| NO (1) | NO314081B1 (fr) |
| NZ (1) | NZ337424A (fr) |
| PL (1) | PL192116B1 (fr) |
| TR (1) | TR199902283T2 (fr) |
| TW (1) | TW555694B (fr) |
| WO (1) | WO1998041508A1 (fr) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9726695D0 (en) | 1997-12-17 | 1998-02-18 | Smithkline Beecham Plc | Novel compounds |
| JP2001521026A (ja) * | 1997-10-24 | 2001-11-06 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 置換イソキノリン誘導体および抗痙攣薬としての使用 |
| GB9817424D0 (en) * | 1998-08-11 | 1998-10-07 | Smithkline Beecham Plc | Novel compounds |
| JP2004517029A (ja) * | 1998-12-03 | 2004-06-10 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | 精神分裂病の処置のためのトピラメート及び関連誘導体 |
| AU778393B2 (en) * | 1999-05-12 | 2004-12-02 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazole carboxamides useful for the treatment of obesity and other disorders |
| FR2795724B1 (fr) * | 1999-07-02 | 2002-12-13 | Sanofi Synthelabo | Nouveaux derives du benzene, un procede pour leur preparation et les compositions pharmaceutiques les contenant |
| GB9915589D0 (en) * | 1999-07-02 | 1999-09-01 | Smithkline Beecham Plc | Novel compounds |
| AR038420A1 (es) * | 2002-02-15 | 2005-01-12 | Glaxo Group Ltd | Compuesto de amida, procedimiento para la preparacion del mismo, su uso para la fabricacion de un medicamento y composicion farmaceutica que lo comprende |
| GB0210762D0 (en) * | 2002-05-10 | 2002-06-19 | Glaxo Group Ltd | Compounds |
| AU2003249534A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 6,6-fused heteroaryl derivatives as matrix metalloproteinase inhibitors |
| GB0226724D0 (en) | 2002-11-15 | 2002-12-24 | Merck Sharp & Dohme | Therapeutic agents |
| EP1632477B1 (fr) | 2003-06-12 | 2017-03-01 | Astellas Pharma Inc. | Derive de benzamide ou sel de ce dernier |
| WO2005032493A2 (fr) | 2003-10-07 | 2005-04-14 | Renovis, Inc. | Composes d'amides utilises en tant que ligands de canaux ioniques et utilisations correspondantes |
| GB2413129A (en) * | 2003-10-07 | 2005-10-19 | Renovis Inc | Aromatic amide compounds as ion channel ligands and uses thereof |
| WO2005072681A2 (fr) * | 2004-01-23 | 2005-08-11 | Amgen Inc. | Ligands des recepteurs vanilloides et utilisation de ceux-ci dans divers traitements |
| WO2006032851A1 (fr) * | 2004-09-20 | 2006-03-30 | Biolipox Ab | Composés de pyrazole utiles dans le traitement d'une inflammation |
| SE0403117D0 (sv) * | 2004-12-21 | 2004-12-21 | Astrazeneca Ab | New compounds 1 |
| PT2046787E (pt) | 2006-08-01 | 2011-06-15 | Glaxo Group Ltd | Compostos de pirazolo[3,4-b]piridina e sua utilização como inibidores de pde4 |
| CN106608901B (zh) * | 2015-10-22 | 2020-10-16 | 彭莉 | 二羟基二甲基四氢异喹啉-3-甲酰-Lys(Lys-Ala),其合成,活性及应用 |
| CN111138359A (zh) * | 2020-01-19 | 2020-05-12 | 浙江农林大学暨阳学院 | 制备3-羰基-4-叠氮基-n-苯磺酰基-1,2,3,4-四氢异喹啉类化合物的方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022900A (en) * | 1970-09-09 | 1977-05-10 | Marion Laboratories, Inc. | Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents |
| EP0906283A1 (fr) * | 1996-06-17 | 1999-04-07 | Smithkline Beecham Plc | Derives substitues du benzamide et leur utilisation comme anticonvulsivants |
-
1998
- 1998-03-16 CA CA002284218A patent/CA2284218A1/fr not_active Abandoned
- 1998-03-16 PL PL335676A patent/PL192116B1/pl unknown
- 1998-03-16 EP EP98909647A patent/EP0968190A1/fr not_active Withdrawn
- 1998-03-16 NZ NZ337424A patent/NZ337424A/en unknown
- 1998-03-16 KR KR1019997008443A patent/KR100568654B1/ko not_active Expired - Fee Related
- 1998-03-16 WO PCT/GB1998/000782 patent/WO1998041508A1/fr not_active Ceased
- 1998-03-16 IL IL13175698A patent/IL131756A0/xx active IP Right Grant
- 1998-03-16 CN CNB988048809A patent/CN1183116C/zh not_active Expired - Fee Related
- 1998-03-16 BR BR9809047-0A patent/BR9809047A/pt not_active Application Discontinuation
- 1998-03-16 AU AU64128/98A patent/AU737955B2/en not_active Ceased
- 1998-03-16 TR TR1999/02283T patent/TR199902283T2/xx unknown
- 1998-03-16 JP JP54024898A patent/JP3690423B2/ja not_active Expired - Fee Related
- 1998-03-17 AR ARP980101199A patent/AR012092A1/es unknown
- 1998-03-18 CO CO98015157A patent/CO4950553A1/es unknown
- 1998-03-20 TW TW087104135A patent/TW555694B/zh not_active IP Right Cessation
-
1999
- 1999-09-17 NO NO19994510A patent/NO314081B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001515504A (ja) | 2001-09-18 |
| AU737955B2 (en) | 2001-09-06 |
| NO994510D0 (no) | 1999-09-17 |
| EP0968190A1 (fr) | 2000-01-05 |
| NO994510L (no) | 1999-09-17 |
| TR199902283T2 (xx) | 1999-12-21 |
| IL131756A0 (en) | 2001-03-19 |
| PL192116B1 (pl) | 2006-08-31 |
| PL335676A1 (en) | 2000-05-08 |
| AU6412898A (en) | 1998-10-12 |
| KR100568654B1 (ko) | 2006-04-07 |
| CN1255124A (zh) | 2000-05-31 |
| BR9809047A (pt) | 2000-08-01 |
| TW555694B (en) | 2003-10-01 |
| CN1183116C (zh) | 2005-01-05 |
| NZ337424A (en) | 2001-08-31 |
| JP3690423B2 (ja) | 2005-08-31 |
| NO314081B1 (no) | 2003-01-27 |
| KR20000076342A (ko) | 2000-12-26 |
| AR012092A1 (es) | 2000-09-27 |
| CO4950553A1 (es) | 2000-09-01 |
| WO1998041508A1 (fr) | 1998-09-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |