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US 6,274,593 B1Granted
Substituted tetrahydro isoquinolines as modulators of dopamine D3 receptors
AssigneeSmithKline Beecham Corporation
InventorsAmanda Johns, David John Nash, Geoffrey Stemp
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of formula (I): which are useful as antipsychotic agents.
Claims11
A compound of formula (I):
- wherein:
- R1 represents a substituent selected from:
- a hydrogen or halogen atom;
- a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, pentafluoroethyl, C1-4alkyl, C1-4alkoxy, arylC1-4alkoxy, C1-4alkylthio, C1-4alkoxyC1-4alkyl, C3-6cycloalkylC1-4alkoxy, C1-4alkanoyl, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4alkylsulphonyloxy, C1-4alkylsulphonylC1-4alkyl, arylsulphonyl, arylsulphonyloxy, arylsulphonylC1-4alkyl, C1-4alkylsulphonamido, C1-4alkylamido, C1-4alkylsulphonamidoC1-4alkyl, C1-4alkylamidoC1-4alkyl, arylsulphonamido, arylcarboxamido, arylsulphonamidoC1-4alkyl, arylcarboxamidoC1-4alkyl, aroyl, aroylC1-4alkyl, or arylC1-4alkanoyl group;
- a group R3OCO(CH2)p, R3CON(R4)(CH2)p, R3R4NCO(CH2)p or R3R4NSO2(CH2)p where each of R3 and R4 independently represents a hydrogen atom or a C1-4alkyl group or R3R4 forms part of a C3-6azacyloalkane or C3-6(2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4;
- or a group Ar3—Z, wherein Ar3 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring and Z represents a bond, O, S, or CH2;
- R2 represents a hydrogen atom or a C1-4alkyl group;
- X represents a group of the formula (a) or (b):
- wherein
- Ar and Ar1 each independently represent an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring;
- and
- Y represents a bond, —NHCO—, —CONH—, —CH2—, or —(CH2)mY1(CH2)n—, wherein Y1 represents O, S, SO2, or CO and m and n each represent zero or 1 such that the sum of m+n is zero or 1;
- Ar2 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring;
- or an optionally substituted bicyclic ring system;
- or a salt thereof.
12 more elements
A compound of formula (I) which is:
- (E)-2-(4-(3-(2-Naphthyl)propenoyl)aminobutyl)-6-trifluoromethoxy-1,2,3,4-tetrahydroisoquinoline;
- (E)-2-(4-(3-(5-Indolyl)propenoyl)aminobutyl)-6-trifluoromethoxy-1,2,3,4-tetrahydroisoquinoline;
- (E)-2-(4-(3-(5-Benzimidazolyl)propenoyl)aminobutyl)-6-trifluoromethoxy-1,2,3,4-tetrahydroisoquinoline;
- (E)-2-(4-(3-(5-Indolyl)propenoyl)aminobutyl)-6-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Cyano-2-(4-(3-(5-indolyl)propenoyl)aminobutyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Cyano-2-(4-(3-(5-benzimidazolyl)propenoyl)aminobutyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(2-naphthyl)propenoyl)aminobutyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(5-indolyl)propenoyl)(aminobutyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(5-(2-methyl)indolylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(6-indolylpropenoyl)amino)butyl)-1,2,3,4,-tetrahydroisoquinoline;
- (E)-6-Chloro-2-(4-(3-(5-indolylpropenoyl)amino)butyl)-1,2,3,4,-tetrahydroisoquinoline;
- (E)-6-Chloro-2-(4-(3-(2-naphythylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(5-(3-methyl)indolylpropenoyl)aminobutyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Chloro-2-(4-(3-(6-indolylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-2-(4-(3-(5-(3-Acetyl)indolylpropenoyl)amino)butyl)-6-bromo-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(6-(2-methyl)indolylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2(4-(3-(5-(2-methyl)-1H-benzimidazolylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- (E)-6-Bromo-2-(4-(3-(5-( 1-methyl)indolylpropenoyl)amino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- 2-(4-(4-(4-Actylphenyl)benzoylamino)butyl)-6-trifluoromethoxy-1,2,3,4-tetrahydroisoquinoline;
- 6-Methoxy-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- 6-Hydroxy-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinoline;
- 2-(4-(4-phenylbenzoylamino)butyl)-6-trifluoromethylsulfonyloxy-1,2,3,4-tetrahydroisoquinoline;
- or a salt thereof.
20 more elements
Dependencies are inferred from the claim text.