US 6,638,962 B2 · Cycloheptene compounds

Abstract

Compound of formula (I): wherein: X represents a bond or alkylene, CO, S(O)n, —S(O)n—A1—, —CO—A1—, —A—S(O)n—A′1— or —A1—CO—A′1—, Y represents aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, R1, R2, R3 and R4 each independently of the others represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, or R1, R2, R3 and R4, taken in pairs, together form a bond, or form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle, T represents —CH(R5)—, —N(R5)— or —N(R5)CO—, V represents hydrogen or unsubstituted or substituted aryl or heteroaryl, A2 represents [C(R6)(R′6)]p, R7 and R8 are as defined in the description, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as farnesyl transferase inhibitors.

A Compound of formula (I):

wherein:
X may be a bond or a group selected from alkylene, CO, S(O)n, *—S(O)n—A1—, *—CO—A1—, —A1—S(O)n—A′1— and —A1—CO—A′1— (wherein A1 and A′1, which may be identical or different, represent alkylene and n is 0, 1 or 2), the symbol “*” indicating the point of attachment of those groups to the cycloheptene,
Y is selected from aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each of those groups being unsubstituted or substituted by one or more, identical or different, R8 groups,
R1, R2, R3 and R4 independently represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of those groups being unsubstituted or substituted by one or more, identical or different, R8 groups.
or R1, R2, R3 and R4, taken in pairs, together form a bond,
or R1 and R2, or R2 and R3, or R3 and R4, taken in pairs with the carbon atoms to which they are bonded, form fused benzene or a fused aromatic or partially unsaturated heterocycle, having 5 or 6 ring members and containing 1 or 2 hetero atoms selected from nitrogen, oxygen and sulphur, with the understanding that only one ring can be fused on the 7-membered structure,
T is selected from —CH(R5)—, —N(R5)— and *—N(R5)CO— (wherein R5 is selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, each of those groups being unsubstituted or substituted by one or more, identical or different, R7 groups), the symbol “*” indicating the point of attachment of the group to the cycloheptene,
V is selected from hydrogen, aryl, and heteroaryl, each of those groups being unsubstituted or substituted by one or more, identical or different, R7 groups,
A2 may be [C(R6)(R′6)]p wherein p is 0, 1, 2, 3 or 4 when T represents —CH(R5)— or *—N(R5)CO—, or p is 1, 2, 3 or 4 when T represents —N(R5)—;
and R6and R′6, which may be identical or different, represent hydrogen or alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or optionally substituted heterocycloalkylalkyl group, R9 or alkyl substituted by R9 (wherein R9 represents —OR5, —N(R5)(R′5), —S(O)R5, —CON(R5)(R′5), —N(R5)COR′5, —N(R5)SO2R′5, —SO2N(R5)(R′5) or —N(R5)COO(R′5), m being 0, 1 or 2, and R′5 can have any of the meanings of R5),
R7 may be halogen or alkyl, alkoxy, hydroxy, mercapto, alkylthio, cyano, amino (optionally substituted by one or two alkyl groups), nitro, carboxy, alkoxycarbonyl, aminocarbonyl (optionally substituted by one or two alkyl groups), carbamoyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heterocycloalkyl or unsubstituted or substituted heterocycloalkylalkyl group,
R8 may be halogen, or oxo, hydroxy, cyano, nitro, carboxy, alkoxycarbonyl or perhaloalkyl or —U-R80 or —A80-U—R80 (wherein A80 represents alkylene;
U represents a bond, oxygen or a group selected from NH, S(O)m, NHCO, CONH, SO2NH and NHSO2, m being 0, 1 or 2;
and R80 is a group selected from alkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl),
it being understood that:
the term “alkyl” denotes a linear or branched group containing from 1 to 6 carbon atoms,
the term “alkylene” denotes a linear or branched bivalent group containing from 1 to 6 carbon atoms,
the term “cycloalkyl” denotes a saturated cyclic group containing from 3 to 8 carbon atoms,
the term “heterocycloalkyl” denotes a saturated or partially unsaturated cyclic group having from 5 to 7 ring members and containing from 1 to 3 hetero atoms selected from nitrogen, oxygen and sulphur,
the term “aryl” denotes a phenyl or naphthyl group,
the term “heteroaryl” denotes a mono- or bi-cyclic group that is aromatic or contains at least one aromatic ring, has from 5 to 11 ring members and contains from 1 to 5 hetero atoms selected from nitrogen, oxygen and sulphur,
the term “substituted” applied to the terms “aryl”, “heteroaryl”, “cycloalkyl” and “heterocycloalkyl” means that those groups may be substituted by one or more identical or different groups selected from cyano, alkylcarbonyl, aminocarbonyl (optionally substituted by one or two alkyl groups) and halogen atoms,
the term “substituted” applied to the terms “arylalkyl”, “heteroarylalkyl”, “cycloalkylalkyl” and “heterocycloalkylalkyl” means that the cyclic moiety of those groups may be substituted by one or more identical or different groups selected from oxo, cyano, alkylcarbonyl, aminocarbonyl (optionally substituted by one or two alkyl groups) and halogen atoms,
provided that when T is N(R5), then R1, R2, R3, and R4, taken in pairs, may not together form a bond,
its enantiomers, diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

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Cycloheptene compounds

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Cycloheptene compounds

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Abstract

Claims21