Patent ID: 6525047
Filing Date: 2003-02-25
Classification: A61K,A61P,C07D,C07K

Abstract:
A compound of the formula or a stereoisomeric mixture thereof, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomer thereof, or a prodrug of such compound, mixture or isomer thereof, or a pharmaceutically acceptable salt of the compound, mixture, isomer or prodrug,whereinHET is a heterocyclic moiety selected from the group consisting of Q is a covalent bond or CH2; X is CH2, C&boxH;CH2 or C&boxH;O; Y is CH2, O or NR2; Z is C&boxH;O; R1 is hydrogen, â€”CN, â€”(CH2)qN(X6)C(O)X6, â€”(CH2)q N(X6)C(O)(CH2)tâ€”A1, â€”(CH2)qN(X6)S(O)2(CH2)tâ€”A1, â€”(CH2)qN(X6)S(O)2X6, â€”(CH2)q N(X6)C(O)N(X6)(CH2)t â€”A1, â€”(CH2)q N(X6)C(O)N(X6)(X6), â€”(CH2)q C(O)N(X6)(X6), â€”(CH2)q C(O)N(X6)(CH2)tâ€”A1, â€”(CH2)qC(O)0X6, â€”(CH2)qC(O)O(CH2)tâ€”A1, â€”(CH2)qOX6, â€”(CH2)qOC(O)X6, â€”(CH2)qOC(O)(CH2)tA1, â€”(CH2)qOC(O)N(X6)(CH2)tâ€”A1, â€”(CH2)qOC(O)N(X6)(X6), â€”(CH2)qC(O)X6, â€”(CH2)qC(O)(CH2)tâ€”A1, â€”(CH2)qN(X6)C(O)0X6, â€”(CH2)qN(X6)S(O)2N(X6)(X6), â€”(CH2)qS(O)mX6, â€”(CH2)qS(O)m(CH2)tâ€”A1, â€”(C1-C10)alkyl, â€”(CH2)tâ€”A1, â€”(CH2)qâ€”(C3-C7)cycloalkyl, â€”(CH2)qâ€”Y1 â€”(C1-C6)alkyl, â€”(CH2 )qâ€”Y1â€”(CH2)tâ€”A1 or â€”(CH2)qâ€”Y1 â€”(CH2)tâ€”(C3 -C7)cycloalkyl; where A1 in the definition of R1 is phenyl, pyridyl, thiazolyl or thienyl, optionally substituted with one to three substituents, each substituent being independently selected from the group consisting of F, Cl, CH3, OCH3, OCF2H, OCF3 and CF3; and where the alkyl and cycloalkyl groups in the definition of R1 are optionally substituted with (C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, or 1, 2 or 3 fluoro groups; q is 1 or 2; t is 1 or 2; said (CH2)qgroup and (CH2)t group in the definition of R1 are optionally independently substituted with hydroxy, (C1-C4)alkoxy, carboxyl, â€”CONH2, â€”S(O)m(C1-C6)alkyl, â€”CO2(C1-C4)alkyl ester, 1H-tetrazol-5-yl, 1, 2 or 3 fluoro groups or 1 or 2 (C1-C4)alkyl groups; R2 is hydrogen, (C1-C5)alkyl or (C0-C2)alkylâ€”(C3-C8)cycloalkyl; where the alkyl groups and the cycloalkyl groups in the definition of R2 are optionally substituted with fluoro groups; R3 is phenylâ€”CH2â€”Oâ€”CH2â€”, phenylâ€”CH2â€”Sâ€”CH2â€”, pyridylâ€”CH2â€”Oâ€”CH2â€”, thienylâ€”CH2â€”Oâ€”CH2â€”, thiazolylâ€”CH2â€”Oâ€”CH2â€”, phenylâ€”(CH2)3â€”or 3-indolylâ€”CH2â€”; where the carbon atom bearing the substituent R3 is of the (R) configuration; where the aryl portion of the groups defined for R3 is optionally substituted with one to three substituents, each substituent being independently selected from the group consisting of F, Cl, CH3, OCH3, OCF2H, OCF3 and CF3; R4 is hydrogen; X4 is hydrogen; where a and b are each 0; X5 and X5a are each methyl; Z1 is a bond; R7 and R8 are each hydrogen.