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US 2001/0025045 A1Published application
Substituted isoquinoline derivatives and their use as anticonvulsants
AssigneeSmithKline Beecham Corporation
InventorsPeter David Edwards, John David Harling, Mervyn Thompson
Life of this patent
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Abstract
This invention relates to substituted isoquinoline derivatives and their use as anticonvulsants.
Claims13
A compound of formula (Ia) or pharmaceutically acceptable salt thereof:
- 21
- where n and p are independently integers from 1 to 4 and (n+p) is from 2 to 5;
- R1 is hydrogen, C3-6cycloalkylO— or C3-6cycloalkyl C1-4alkylO—;
- R2 is hydrogen, halogen, CN, N3, trifluoromethyldiazirinyl, C1-6perfluoroalkyl, CF3O—, CF3S—, CF3CO—, C1-6alkyl, C3-6cycloalkyl, CF3SO2—, C3-6cycloalkyl—C1-4alkyl—, C1-6alkylO—, C1-6alkylCO—, C3-6cycloalkylCO—, C3-6cycloalkyl—C1-4alkylCO—, 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
- R3 is hydrogen, halogen, NO2, CN, N3, trifluoromethyldiazirinyl, C1-6 alkylO—, C1-6 alkylS—, C1-6 alkyl, C1-6 hydroxyalkyl, C3-6cycloalkyl, C3-6cycloalkyl—C1-4alkyl—, C1-6alkenyl, C1-6alkynyl, CF3CO—, C1-6alkylCO—, C3-6cycloalkylCO—, C3-6cycloalkyl—C1-4alkylCO—, phenyl, phenoxy, benzyloxy, benzoyl, phenyl—C1-4alkyl—, or —NR5R6 where R5 is hydrogen or C1-4 alkyl, and R6 is hydrogen, C1-4alkyl, —CHO, —CO2C1-4alkyl or —COC1-4alkyl;
- or
- R2 and R3 together form a carbocyclic ring that is unsaturated or saturated and unsubstituted or substituted by carbonyl or hydroxyl;
- R4 is hydrogen, C1-6 alkyl,optionally substituted by hydroxy or C1-4alkoxy;
- C1-6 alkenyl, or C1-6 alkynyl, formyl, C1-6alkylCO , C1-6alkylSO2, or CF3CO—.
6 more elements
A compound of formula (Ib) or pharmaceutically acceptable salt thereof:
- 22
- where n and p are independently integers from 1 to 4 and (n+p) is from 2 to 5;
- R1 is hydrogen, C1-6alkylO—, C3-6cycloalkylO— or C3-6cycloalkyl C1-4alkylO—;
- R2 is CF3SO2—,C2-6perfluoroalkyl, (C1-4alkyl)2NCO—,(C1-4alkyl)NHCO—;or CONH2
- R3 is hydrogen, halogen, NO2, CN, N3, trifluoromethyldiazirinyl, C1-6 alkylO—, C1-6 alkylS—, C1-6 alkyl, C1-6 hydroxyalkyl C3-6cycloalkyl, C3-6cycloalkyl—C1-4alkyl—, C1-6alkenyl, C1-6alkynyl, CF3CO—, C1-6alkylCO—, C3-6cycloalkylCO—, C3-6cycloalkyl—C1-4alkylCO—, phenyl, phenoxy, benzyloxy, benzoyl, phenyl—C. 1-4alkyl—, or —NR5R6 where R5 is hydrogen or C1-4 alkyl, and R6 is hydrogen, C1-4alkyl, —CHO, —CO2C1-4alkyl or —COC1-4alkyl;
- R4 is hydrogen, C1-6 alkyl,optionally substituted by hydroxy or C1-4alkoxy;
- C1-6 alkenyl, or C1-6 alkynyl, formyl, C1-6alkylCO , C1-6alkylSO2, or CF3CO—.
4 more elements
A compound of formula (Ic) or pharmaceutically acceptable salt thereof:
- 23
- where n and p are independently integers from 1 to 4 and (n+p) is from 2 to 5;
- R1 is hydrogen, C1-6alkylO—, C3-6cycloalkylO— or C3-6cycloalkyl C1-4alkylO—;
- R2 and R3 together form a carbocyclic ring that is unsaturated or saturated and unsubstituted or substituted by carbonyl or hydroxyl;
- R4 is hydrogen, C1-6 alkyl,optionally substituted by hydroxy or C1-4alkoxy;
- C1-6 alkenyl, or C1-6 alkynyl, formyl, C1-6alkylCO, C1-6alkylSO2, or CF3CO—.
3 more elements
A compound of formula (Id) or pharmaceutically acceptable salt thereof:
- 24
- where n and p are independently integers from 1 to 4 and (n+p) is from 2 to 5;
- R1 is hydrogen, C1-6alkylO—, C3-6cycloalkylO— or C3-6cycloalkyl C1-4alkylO—;
- R2 is hydrogen, halogen, CN, N3, trifluoromethyldiazirinyl, C1-6perfluoroalkyl, CF3O—, CF3S—, CF3CO—, CF3SO2—,C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl—C4alkyl—, C1-6alkylO—, C1-6alkylCO—, C3-6cycloalkylCO—, C3-6cycloalkyl—C1-4alkylCO—, 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
- R3 is hydrogen, halogen, NO2, CN, N3, trifluoromethyldiazirinyl, C1-6 alkylO—, C1-6 alkylS—, C1-6 alkyl, C1-6 hydroxyalkyl C3-6cycloalkyl, C3-6cycloalkyl—C1-4alkyl—, C1-6alkenyl, C1-6alkynyl, CF3CO—, C1-6alkylCO—, C3-6cycloalkylCO—, C3-6cycloalkyl—C1-4alkylCO—, phenyl, phenoxy, benzyloxy, benzoyl, phenyl—C1-4alkyl—, or —NR5R6 where R5 is hydrogen or C1-4 alkyl, and R6 is hydrogen, C1-4alkyl, —CHO, —CO2C1-4alkyl or —COC1-4alkyl;
- or
- R2 and R3 together form a carbocyclic ring that is unsaturated or saturated and unsubstituted or substituted by carbonyl or hydroxyl;
- R4 is C1-6 alkyl substituted by hydroxy or C1-4alkoxy;
- formyl, C1-6alkylCO, C1-6alkylSO2,or CF3CO—.
6 more elements
A compound according to claim7 in which
- R1 as hydrogen, methoxy, ethoxy, n-propoxy or cyclopropylmethoxy;
- R2 as hydrogen, methoxy, bromo, chloro, iodo, acetyl, pivaloyl, CF3SO2—, iso-butyroyl, benzoyl, trifluoromethyl, trifluoroacetyl, methanesulfonyl, n-propylsulfonyl, isopropylsulfonyl, dimethylsulfamoyl, cyano or perfluoroethyl;
- R3 as hydrogen, methyl, ethyl, n-butyl, iso-propyl, t-butyl, phenyl;
- methoxy, ethoxy, iso-propoxy, n-butoxy, phenoxy, benzyloxy, amino, acetylamino, nitro, benzoyl, iodobenzoyl, chloro or azido;
- or
- R2 and R3 form a benzene, cyclopentane or cyclopentanone ring;
- R4 as acetyl, trifluoroacetyl or methanesulfonyl.
4 more elements
A compound according to any one of the preceding claims which is a compound described in any one of the foregoing Examples.
A compound of formula (I) as hereinbefore defined, substantially as hereinbefore described in any one of the Examples.
Dependencies are inferred from the claim text.