Patent ID: 6278000
Filing Date: 2001-08-21
Classification: A61K,A61P,C07D,C07K

Abstract:
A compound of the formula ##STR51##the racemic-diastereomeric mixtures and optical isomers of said compounds and the pharmaceutically-acceptable salts thereof, whereine is 0;n is 0 and w is 1, or n is 1 and w is 0;R.sup.1 is hydrogen, --CN, --(CH.sub.2).sub.q N(X.sup.6)C(O)X.sup.6, --(CH.sub.2).sub.q N(X.sup.6)C(O)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q N(X.sup.6)SO.sub.2 (CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q N(X.sup.6)SO.sub.2 X.sup.6, --(CH.sub.2).sub.q N(X.sup.6)C(O)N(X.sup.6)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q N(X.sup.6)C(O)N(X.sup.6)(X.sup.6), --(CH.sub.2).sub.q C(O)N(X.sup.6)(X.sup.6), --(CH.sub.2).sub.q C(O)N(X.sup.6)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q C(O)OX.sup.6, --(CH.sub.2).sub.q C(O)O(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q OX.sup.6, --(CH.sub.2).sub.q OC(O)X.sup.6, --(CH.sub.2).sub.q OC(O)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q OC(O)N(X.sup.6)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q OC(O)N(X.sup.6)(X.sup.6), --(CH.sub.2).sub.q C(O)X.sup.6, --(CH.sub.2).sub.q C(O)(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q N(X.sup.6)C(O)OX.sup.6, --(CH.sub.2).sub.q N(X.sup.6)SO.sub.2 N(X.sup.6)(X.sup.6), --(CH.sub.2).sub.q S(O).sub.m X.sup.6, --(CH.sub.2).sub.q S(O).sub.m (CH.sub.2).sub.t -A.sup.1, --(C.sub.1 -C.sub.10)alkyl, --(CH.sub.2).sub.t -A.sup.1, --(CH.sub.2).sub.q --(C.sub.3 -C.sub.7)cycloalkyl, --(CH.sub.2).sub.q --Y.sup.1 --(C.sub.1 -C.sub.6)alkyl, --(CH.sub.2).sub.q --Y.sup.1 --(CH.sub.2).sub.t -A.sup.1 or --(CH.sub.2).sub.q --Y.sup.1 --(CH.sub.2).sub.t --(C.sub.3 -C.sub.7)cycloalkyl;where the alkyl and cycloalkyl groups in the definition of R.sup.1 are optionally substituted with (C.sub.1 -C.sub.4)alkyl, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, carboxyl, CONH.sub.2, --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, --CO.sub.2 (C.sub.1 -C.sub.4)alkyl, 1 H-tetrazol-5-yl or 1 to 3 fluoro;Y.sup.1 is O, S(O).sub.m, --C(O)NX.sup.6, --CH.dbd.CH--, --C.ident.C--, --N(X.sup.6)C(O)--, --C(O)NX.sup.6 --, --C(O)O--, --OC(O)N(X.sup.6)-- or --OC(O)--;q is 0, 1, 2, 3 or 4;t is 0, 1, 2 or 3;said (CH.sub.2).sub.q group and (CH.sub.2).sub.t group may each be optionally substituted with 1 to 3 fluoro, 1 or 2 (C.sub.1 -C.sub.4)alkyl, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, carboxyl, --CONH.sub.2, --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, --CO.sub.2 (C.sub.1 -C.sub.4)alkyl ester, or 1 H-tetrazol-5-yl;R.sup.2 is hydrogen, (C.sub.1 -C.sub.8)alkyl, --(C.sub.0 -C.sub.3)alkyl-(C.sub.3 -C.sub.8)cycloalkyl, --(C.sub.1 -C.sub.4)alkyl-A.sup.1 or A.sup.1 ;where the alkyl groups and the cycloalkyl groups in the definition of R.sup.2 are optionally substituted by hydroxyl, --C(O)OX.sup.6, --C(O)N(X.sup.6)(X.sup.6), --N(X.sup.6)(X.sup.6), --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, --C(O)A.sup.1, --C(O)(X.sup.6), CF.sub.3, CN or 1 to 3 halogen;A.sup.1 for each occurrence is independently (C.sub.5 -C.sub.7)cycloalkenyl, phenyl or a partially saturated, fully saturated or fully unsaturated 4- to 8-membered ring optionally having 1 to 4 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, or a bicyclic ring system consisting of a partially saturated, fully unsaturated or fully saturated 5- or 6-membered ring, optionally having 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen, fused to a partially saturated, fully saturated or fully unsaturated 5- or 6-membered ring, optionally having 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen;A.sup.1 for each occurrence is independently optionally substituted, in one or optionally both rings if A.sup.1 is a bicyclic ring system, with up to three substituents, each substituent independently selected from the group consisting of F, Cl, Br, I, OCF.sub.3, OCF.sub.2 H, CF.sub.3, CH.sub.3, OCH.sub.3, --OX.sup.6, --C(O)N(X.sup.6)(X.sup.6), --C(O)OX.sup.6, oxo, (C.sub.1 -C.sub.6)alkyl, nitro, cyano, benzyl, --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, 1 H-tetrazol-5-yl, phenyl, phenoxy, phenylalkyloxy, halophenyl, methylenedioxy, --N(X.sup.6)(X.sup.6), --N(X.sup.6)C(O)(X.sup.6), --SO.sub.2 N(X.sup.6)(X.sup.6), --N(X.sup.6)SO.sub.2 -phenyl, --N(X.sup.6)SO.sub.2 X.sup.6, --CONX.sup.11 X.sup.12, --SO.sub.2 NX.sup.11 X.sup.12, --NX.sup.6 SO.sub.2 X.sup.12, --NX.sup.6 CONX.sup.11 X.sup.12, --NX.sup.6 SO.sub.2 NX.sup.11 X.sup.12, --NX.sup.6 C(O)X.sup.12, imidazolyl, thiazolyl and tetrazolyl, provided that if A.sup.1 is optionally substituted with methylenedioxy then it can only be substituted by one methylenedioxy;where X.sup.11 is hydrogen or optionally substituted (C.sub.1 -C.sub.6)alkyl;the optionally substituted (C.sub.1 -C.sub.6)alkyl defined for X.sup.11 is optionally independently substituted with phenyl, phenoxy, (C.sub.1 -C.sub.6)alkoxycarbonyl, --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, 1 to 5 halogens, 1 to 3 hydroxy, 1 to 3 (C.sub.1 -C.sub.10)alkanoyloxy or 1 to 3 (C.sub.1 -C.sub.6)alkoxy;X.sup.12 is hydrogen, (C.sub.1 -C.sub.6)alkyl, phenyl, thiazolyl, imidazolyl, furyl or thienyl, provided that when X.sup.12 is not hydrogen, X.sup.12 is optionally substituted with one to three substituents independently selected from the group consisting of Cl, F, CH.sub.3, OCH.sub.3, OCF.sub.3 and CF.sub.3 ;or X.sup.11 and X.sup.12 are taken together to form --(CH.sub.2).sub.r -L.sup.1 -(CH.sub.2).sub.r --;L.sup.1 is C(X.sup.2)(X.sup.2), O, S(O).sub.m or N(X.sup.2);r for each occurrence is independently 1, 2 or 3;X.sup.2 for each occurrence is independently hydrogen, optionally substituted (C.sub.1 -C.sub.6)alkyl, or optionally substituted (C.sub.3 -C.sub.7)cycloalkyl, where the optionally substituted (C.sub.1 -C.sub.6)alkyl and optionally substituted (C.sub.3 -C.sub.7)cycloalkyl in the definition of X.sup.2 are optionally independently substituted with --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, --C(O)OX.sup.3, 1 to 5 halogens or 1 to 3 OX.sup.3 ;X.sup.3 for each occurrence is independently hydrogen or (C.sub.1 -C.sub.6)alkyl;X.sup.6 for each occurence is independently hydrogen, optionally substituted (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)halogenated alkyl, optionally substituted (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.3 -C.sub.7)-halogenatedcycloalkyl, where optionally substituted (C.sub.1 -C.sub.6)alkyl and optionally substituted (C.sub.3 -C.sub.7)cycloalkyl in the definition of X.sup.6 is optionally independently substituted with, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, carboxyl, CONH.sub.2, --S(O).sub.m (C.sub.1 -C.sub.6)alkyl, --CO.sub.2 (C.sub.1 -C.sub.4)alkyl, 1 H-tetrazol-5-yl or 1 or 2 (C.sub.1 -C.sub.4)alkyl; orwhere there are two X.sup.6 groups on one atom and both X.sup.6 are (C.sub.1 -C.sub.6)alkyl, the two (C.sub.1 -C.sub.6)alkyl groups may be optionally joined and, together with the atom to which the two X.sup.6 groups are attached, form a 4- to 9-membered ring optionally having oxygen, sulfur or NX.sup.7 ;X.sup.7 is hydrogen or (C.sub.1 -C.sub.6)alkyl optionally substituted with hydroxyl; andm for each occurrence is independently 0, 1 or 2;with the proviso that:X.sup.6 and X.sup.12 cannot be hydrogen when it is attached to C(O) or SO.sub.2 in the form C(O)X.sup.6, C(O)X.sup.12, SO.sub.2 X.sup.6 or SO.sub.2 X.sup.12 ; andwhen R.sup.2 is hydrogen then R.sup.1 is not --CH.dbd.CH-phenyl.