US 2003/0144320 A1Published application

Substituted isoquinoline derivatives and their use as anticonvulsants

AssigneeSmithKline Beecham Corporation

InventorsMervyn Thompson, Robert William Ward, Peter David Edwards

Life of this patent

Estimating the term…

Abstract

This invention relates to substituted isoquinoline derivatives and their use as anticonvulsants.

Claims7

Dependent claims

A compound of formula (I) or a pharmaceutically acceptable salt thereof:

10
where Q is a monocyclic or bicyclic aryl or heteroaryl ring,
R1 is hydrogen, C1-6 alkyl (optionally substituted by hydroxy or C1-4alkoxy), C1-6alkenyl, C1-6alkynyl, C1-6alkylCO-, formyl, CF3CO— or C1-6alkylSO2—,
R2 is hydrogen, hydroxy or up to three substituents selected from halogen, NO2, CN, N3, CF3O—, CF3S—, CF3CO—, trifluoromethyldiazirinyl, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkylO—, C1-6alkylCO—, C3-6cycloalkylO—, C3-6cycloalkylCO—, C3-6cycloalkyl-C1-4alkylO—, C3-6cycloalkyl-C1-4alkylCO—, acetoxy, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1-6alkylS—, C1-6alkylSO2—, (C1-4alkyl)2NSO2—, (C1-4alkyl)NHSO2—, (C1-4alkyl)2NCO—, (C1-4alkyl)NHCO— or CONH2;
or —NR3R4 where R3 is hydrogen or C1-4 alkyl, and
R4 is hydrogen, C1-4alkyl, formyl, —CO2C1-4alkyl or —COC1-4alkyl;
or two R2 groups together form a carbocyclic ring that is saturated or unsaturated and unsubstituted or substituted by —OH or ═O;
and
X is hydrogen, halogen, C1-6 alkoxy, C1-6 alkyl, amino or trifluoroacetylamino;
but when X is hydrogen excluding compounds in which R2 is 2-alkoxy and when X is halogen excluding the compounds N-(7-iodo-2-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-benzoyl-2-methoxybenzamide, N-(7-iodo-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-benzoyl-2-methoxybenzamide, N-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-benzoyl-2-methoxybenzamide, N-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-methoxy-4-trifluoromethyldiazirinylbenzamide, N-(5-iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-methoxy-5-trifluoromethyldiazirinylbenzamide, N-(7-iodo-1,2,3,4-tetrahydroisoquinolin-5-yl)-2-methoxy-5-trifluoromethyldiazirinyl benzamide and N-(8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-4-t-butyl-2-methoxybenzamide.

7 more elements

A compound selected from the group consisting of:

N-(1,2,3,4-tetrahydroisoquinolin-7-yl)-5-chlorothiophene-2-carboxamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-chlorothiophene-2-carboxamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chlorobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-t-butylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-iso-propoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-phenoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-nitrobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-phenylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-fluorobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyanobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,4-dichlorobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-iodobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-bromobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-nitrobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-ethoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-n-butylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-acetoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-trifluoromethylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2,4-difluorobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,4-dimethoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-fluoro-4-trifluoromethyl benzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-chloro-3-nitrobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,5-di-trifluoromethylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2,4-dichloro-5-fluorobenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-fluoro-5-trifluoromethyl benzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-methoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,4,5-trimethoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-trifluoromethoxybenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-pivaloylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-iso-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-acetoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-cyclopentyloxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-cyclopropylmethoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-naphthamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-methybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-naphthalene-1-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-tert-butoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-n-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl) benzotriazole-5-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)benzothiazole-6-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2,3-dihydrobenzofuran-5-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-methylbenzimidazole-5-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-iso-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-ethoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethyl benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,5-dichloro-4-methoxybenzamide
N-(2-Methyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,5-dichloro-4-ethoxybenzamide
N-(2-Methyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,5-dichloro-4-iso-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methylsulfonylbenzamide
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-tert-butylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-bromo-5-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-fluoro-3-methoxybenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methylpyrazole-4-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-trifluoromethylpyrazole-3-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-methylthiazole-4-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-methylisoxazole-3-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-tert-butylisoxazole-3-carboxamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methoxyisoxazole-5-carboxamide hydrochloride
N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)indole-2-carboxamide.
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-iso-propylbenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-iso-propylbenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-fluoro-4-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-n-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-ethoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-n-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-iodo-4-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-iso-propoxy-3-trifluoromethyl benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-chloro-3-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-n-propoxy-3-trifluoromethyl benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-tert-butylbenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxybenzamide hydrochloride.
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-fluoro-3-methylbenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-iso-propylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-ethylbenzamide hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-iso-propyl-3-trifluoromethyl-benzamide hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-ethyl-3-trifluoromethylbenzamide hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-iso-propoxybenzamide hydrochloride
N-(1,2,3,4-Tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methyl-3-methylsulfonyl-benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methylsulfonylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methylsulfonyl-4-iso-propylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-methylsulfonyl-4-methoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-trifluoroacetylbenzamide, hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-pentafluoroethyl-benzamide hydrochloride
N-(2-n-Propyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-n-Propyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(2-n-Propyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-iso-propoxybenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-cyano-4-iso-butylbenzamide hydrochloride
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-iso-butyl-3-trifluoromethyl-benzamide hydrochloride
N-(2-Ethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-Ethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-4-methoxy-3-trifluoromethyl benzamide
N-(2-iso-Propyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-iso-Propyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethyl benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-ethoxy-3-methylsulfonyl-benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-oxochroman-6-carboxamide hydrochloride
N-(2-Formyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(2-Hydroxyethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-Hydroxyethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethylbenzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-phenylmethoxy-3-trifluoromethyl benzamide
N-(2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-hydroxy-3-trifluoromethyl benzamide
N-(2-Methoxyethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-iso-propoxybenzamide
N-(2-Methoxyethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-chloro-4-iso-propoxybenzamide
N-(2-Methoxyethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(5-Iodo-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-azidobenzamide, trifluoroacetate
N-(2-Methyl-5-trifluoroacetylamino-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-methoxybenzamide
N-(2-Methyl-5-chloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethoxybenzamide
N-(2-Methyl-5-chloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-bromo-4-ethylbenzamide

111 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/353,498Filed 29 Jan 2003
Priority: GB 9705619.618 Mar 1997
Published: 31 Jul 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 217/02
Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems: with only hydrogen atoms or radicals containing only…
C07D 217/04
With only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing…
C07D 217/06
With only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing…

Family

Application09/381,408Continuation · filed 17 Sep 1999
Application09/381,408A 371 of international · filed 17 Sep 1999
Application09/840,786Continuation · filed 24 Apr 2001
Application10/353,498Continuation · filed 29 Jan 2003
US 2001/0016657 A1Published application
US 6,841,560 B2Related patent
US 2003/0144320 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Facts

Application

10/353,498Filed 29 Jan 2003

Priority

GB 9705619.618 Mar 1997

Published

31 Jul 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 217/02
Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems: with only hydrogen atoms or radicals containing only…
C07D 217/04
With only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing…
C07D 217/06
With only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing…

Family

Application09/381,408Continuation · filed 17 Sep 1999

Application09/381,408A 371 of international · filed 17 Sep 1999

Application09/840,786Continuation · filed 24 Apr 2001

Application10/353,498Continuation · filed 29 Jan 2003

US 2001/0016657 A1Published application

US 6,841,560 B2Related patent

US 2003/0144320 A1This patent

From the US filing history. Foreign family members aren’t listed.