Patent ID: 6268378
Filing Date: 2001-07-31
Classification: A61K,C07D

Abstract:
A compound of the formula ##STR43##wherein W is ##STR44##X is selected from the group consisting of--(CH.sub.2).sub.v --, wherein any methylene (CH.sub.2) carbon atom is either unsubstituted or substituted with one or two R.sup.1 substitutents;and a 5- or 6-membered monocyclic aromatic or nonaromatic ring system having 0, 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O, and S wherein the ring nitrogen atoms are unsubstituted or substituted with one R.sup.1 substituent and the ring carbon atoms are unsubstituted or substituted with one or two R.sup.1 substituents;Y is selected from the group consisting of--(CH.sub.2).sub.m --,--(CH.sub.2).sub.m --O--(CH.sub.2).sub.n --,--(CH.sub.2).sub.m --NR.sup.4 --(CH.sub.2).sub.n --,--(CH.sub.2).sub.m --S--(CH.sub.2).sub.n --,--(CH.sub.2).sub.m --SO--(CH.sub.2).sub.n --,--(CH.sub.2).sub.m --SO.sub.2 --(CH.sub.2).sub.n --,--(CH.sub.2).sub.m --O--(CH.sub.2).sub.n --O--(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --O--(CH.sub.2).sub.n --NR.sup.4 --(CH.sub.2).sub.p --.--(CH.sub.2).sub.m --NR.sup.4 --(CH.sub.2).sub.n --NR.sup.4 --(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --O--(CH.sub.2).sub.n --S--(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --S--(CH.sub.2).sub.n --S--(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --NR.sup.4 --(CH.sub.2).sub.n --S--(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --NR.sup.4 --(CH.sub.2).sub.n --O--(CH.sub.2).sub.p --,--(CH.sub.2).sub.m --S--(CH.sub.2).sub.n --O--(CH.sub.2).sub.p --, and--(CH.sub.2).sub.m --S--(CH.sub.2).sub.n --NR.sup.4 --(CH.sub.2).sub.p --,wherein any methylene (CH.sub.2) carbon atom in Y, other than in R.sup.4, can be substituted by one or two R.sup.3 substituents;Z is a 5-membered aromatic or nonaromatic mono- or bicyclic ring system having one heteroatom selected from the group consisting of N, O, and S, and wherein the ring system is either unsubstituted or substituted with 0, 1, 2, or 3 oxo or thio substituents, and either unsubstituted or substituted with one or more substituents independently selected from the group consisting of R.sup.10, R.sup.11, and R.sup.12 ;wherein R.sup.1 is selected from the group consisting ofhydrogen, halogen, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloheteroalkyl, C.sub.3-8 cycloalkyl C.sub.1-6 alkyl, C.sub.3-8 cycloheteroalkyl C.sub.1-6 alkyl, aryl, aryl C.sub.1-8 alkyl, amino, amino C.sub.1-8 alkyl, C.sub.1-3 acylamino, C.sub.1-3 acylamino C.sub.1-8 alkyl, (C.sub.1-6 alkyl).sub.p amino, (C.sub.1-6 alkyl).sub.p amino C.sub.1-8 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxy C.sub.1-6 alkyl, hydroxycarbonyl, hydroxycarbonyl C.sub.1-6 alkyl, C.sub.1-3 alkoxycarbonyl, C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl, hydroxycarbonyl-C.sub.1-6 alkyloxy, hydroxy, hydroxy C.sub.1-6 alkyl, C.sub.1-6 alkyloxy-C.sub.1-6 alkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, trifluoroethoxy, C.sub.1-8 alkyl-S(O).sub.p, (C.sub.1-8 alkyl).sub.p aminocarbonyl, C.sub.1-8 alkyloxycarbonylamino, (C.sub.1-8 alkyl).sub.p aminocarbonyloxy, (aryl C.sub.1-8 alkyl).sub.p amino, (aryl).sub.p amino, aryl C.sub.1-8 alkylsulfonylamino, and C.sub.1-8 alkylsulfonylamino; or two R.sup.1 substituents, when on the same carbon atom, are taken together with the carbon atom to which they are attached to form a carbonyl group;each R.sup.3 is independently selected from the group consisting ofhydrogen,aryl,C.sub.1-10 alkyl,aryl-(CH.sub.2).sub.r --O--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r S(O).sub.p --(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --C(O)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --C(O)--N(R.sup.4)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --N(R.sup.4)--C(O)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --N(R.sup.4)--(CH.sub.2).sub.s --,halogen,hydroxyl,oxo,trifluoromethyl,C.sub.1-8 alkylcarbonylamino,aryl C.sub.1-5 alkoxy,C.sub.1-5 alkoxycarbonyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl,C.sub.1-6 alkylcarbonyloxy,C.sub.3-8 cycloalkyl,(C.sub.1-6 alkyl).sub.p amino,amino C.sub.1-6 alkyl,arylaminocarbonyl,aryl C.sub.1-5 alkylaminocarbonyl,aminocarbonyl,aminocarbonyl C.sub.1-6 alkyl,hydroxycarbonyl,hydroxycarbonyl C.sub.1-6 alkyl,HC.ident.C--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-C.ident.C--(CH.sub.2).sub.t --,C.sub.3-7 cycloalkyl-C.ident.C--(CH.sub.2).sub.t --,aryl-C.ident.C--(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-C.ident.C--(CH.sub.2).sub.t --,CH.sub.2.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.3-7 cycloalkyl-CH.dbd.CH--(CH.sub.2).sub.t --,aryl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-SO.sub.2 --(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-SO.sub.2 --(CH.sub.2).sub.t --,C.sub.1-6 alkoxy,aryl C.sub.1-6 alkoxy,aryl C.sub.1-6 alkyl,(C.sub.1-6 alkyl).sub.p amino C.sub.1-6 alkyl,(aryl).sub.p amino,(aryl).sub.p amino C.sub.1-6 alkyl,(aryl C.sub.1-6 alkyl).sub.p amino,(aryl C.sub.1-6 alkyl).sub.p amino C.sub.1-6 alkyl,arylcarbonyloxy,aryl C.sub.1-6 alkylcarbonyloxy,(C.sub.1-6 alkyl).sub.p aminocarbonyloxy,C.sub.1-8 alkylsulfonylamino,arylsulfonylamino,C.sub.1-8 alkylsulfonylamino C.sub.1-6 alkyl,arylsulfonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylsulfonylamino,aryl C.sub.1-6 alkylsulfonylamino C.sub.1-6 alkyl,C.sub.1-8 alkoxycarbonylamino,C.sub.1-8 alkoxycarbonylamino C.sub.1-8 alkyl,aryloxycarbonylamino C.sub.1-8 alkyl,aryl C.sub.1-8 alkoxycarbonylamino,aryl C.sub.1-8 alkoxycarbonylamino C.sub.1-8 alkyl,C.sub.1-8 alkylcarbonylamino,C.sub.1-8 alkylcarbonylamino C.sub.1-6 alkyl,arylcarbonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylcarbonylamino,aryl C.sub.1-6 alkylcarbonylamino C.sub.1-6 alkyl,aminocarbonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminocarbonylamino,(C.sub.1-8 alkyl).sub.p aminocarbonylamino C.sub.1-6 alkyl,(aryl).sub.p aminocarbonylamino C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminocarbonylamino,(aryl C.sub.1-8 alkyl).sub.p aminocarbonylamino C.sub.1-6 alkyl,aminosulfonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminosulfonylamino,(C.sub.1-8 alkyl).sub.p aminosulfonylamino C.sub.1-6 alkyl,(aryl).sub.p aminosulfonylamino C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminosulfonylamino,(aryl C.sub.1-8 alkyl).sub.p aminosulfonylamino C.sub.1-6 alkyl,C.sub.1-6 alkylsulfonyl,C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,arylsulfonyl C.sub.1-6 alkyl,aryl C.sub.1-6 alkylsulfonyl,aryl C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,C.sub.1-6 alkylcarbonyl,C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,arylcarbonyl C.sub.1-6 alkyl,aryl C.sub.1-6 alkylcarbonyl,aryl C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,C.sub.1-6 alkylthiocarbonylamino,C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,arylthiocarbonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylthiocarbonylamino,aryl C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl C.sub.1-6 alkyl,(aryl).sub.p aminocarbonyl C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminocarbonyl, and(aryl C.sub.1-8 alkyl).sub.p aminocarbonyl C.sub.1-6 alkyl,or two R.sup.3 substituents, when on the same carbon atom are taken together with the carbon atom to which they are attached to form a carbonyl or a cyclopropyl group,wherein any of the alkyl groups of R.sup.3 are either unsubstituted or substituted with one to three R.sup.1 substituents, and provided that each R.sup.3 is selected such that in the resultant compound the carbon atom or atoms to which R.sup.3 is attached is itself attached to no more than one heteroatom;each R.sup.4 is independently selected from the group consisting ofhydrogen,aryl,aminocarbonyl,C.sub.3-8 cycloalkyl,amino C.sub.1-6 alkyl,(aryl).sub.p aminocarbonyl,(aryl C.sub.1-5 alkyl).sub.p aminocarbonyl,hydroxycarbonyl C.sub.1-6 alkyl,C.sub.1-8 alkyl,aryl C.sub.1-6 alkyl,(C.sub.1-6 alkyl).sub.p amino C.sub.2-6 alkyl,(aryl C.sub.1-6 alkyl).sub.p amino C.sub.2-6 alkyl,C.sub.1-8 alkylsulfonyl,C.sub.1-8 alkoxycarbonyl,aryloxycarbonyl,aryl C.sub.1-8 alkoxycarbonyl,C.sub.1-8 alkylcarbonyl,arylcarbonyl,aryl C.sub.1-6 alkylcarbonyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl,aminosulfonyl,C.sub.1-8 alkylaminosulfonyl,(aryl).sub.p aminosulfonyl,(aryl C.sub.1-8 alkyl).sub.p aminosulfonyl,arylsulfonyl,arylC.sub.1-6 alkylsulfonyl,C.sub.1-6 alkylthiocarbonyl,arylthiocarbonyl, andaryl C.sub.1-6 alkylthiocarbonyl,wherein any of the alkyl groups of R.sup.4 are either unsubstituted or substituted with one to three R.sup.1 substituents;R.sup.5 and R.sup.6 are each independently selected from the group consisting ofhydrogen andaryl, wherein aryl is a 6-membered monocyclic or 6,6-bicyclic ring system comprising at least one aromatic ring wherein the monocyclic or bicyclic ring system contains 2, 3, or 4 heteroatoms selected from the group consisting of O, S, and N;R.sup.7 and R.sup.8 are each independently selected from the group consisting ofhydrogen andaryl, wherein aryl is a 6-membered monocyclic or 6,6-bicyclic ring system comprising at least one aromatic ring wherein the monocyclic or bicyclic ring system contains 2, 3, or 4 heteroatoms selected from the group consisting of O, S, and N;R.sup.9 is selected from the group consisting ofhydrogen,C.sub.1-8 alkyl,aryl,aryl C.sub.1-8 alkyl,C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyl,aryl C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyl,C.sub.1-8 alkylaminocarbonylmethylene, andC.sub.1-8 dialkylaminocarbonylmethylene;R.sup.10, R.sup.11, and R.sup.12 are each independently selected from the group consisting ofhydrogen,C.sub.1-8 alkyl,aryl,halogen,hydroxyl,oxo,aminocarbonyl,C.sub.3-8 cycloalkyl,amino C.sub.1-6 alkyl,(aryl).sub.p aminocarbonyl,hydroxycarbonyl,(aryl C.sub.1-5 alkyl).sub.p aminocarbonyl,hydroxycarbonyl C.sub.1-6 alkyl,aryl C.sub.1-6 alkyl,(C.sub.1-6 alkyl).sub.p amino C.sub.1-6 alkyl,(aryl C.sub.1-6 alkyl).sub.p amino C.sub.2-6 alkyl,C.sub.1-8 alkylsulfonyl,C.sub.1-8 alkoxycarbonyl,aryloxycarbonyl,aryl C.sub.1-8 alkoxycarbonyl,C.sub.1-8 alkylcarbonyl,arylcarbonyl,aryl C.sub.1-6 alkylcarbonyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl,aminosulfonyl,C.sub.1-8 alkylaminosulfonyl,(aryl).sub.p aminosulfonyl,(aryl C.sub.1-8 alkyl).sub.p aminosulfonyl,C.sub.1-6 alkylsulfonyl,arylsulfonyl,aryl C.sub.1-6 alkylsulfonyl,aryl C.sub.1-6 alkylcarbonyl,C.sub.1-6 alkylthiocarbonyl,arylthiocarbonyl,aryl C.sub.1-6 alkylthiocarbonyl,aryl-(CH.sub.2).sub.r --O--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r S(O).sub.p --(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --C(O)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --C(O)--N(R.sup.4)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --N(R.sup.4)--C(O)--(CH.sub.2).sub.s --,aryl-(CH.sub.2).sub.r --N(R.sup.4)--(CH.sub.2).sub.s --,HC.ident.C--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-C.ident.C--(CH.sub.2).sub.t --,C.sub.3-7 cycloalkyl-C.ident.C--(CH.sub.2).sub.t --,aryl-C.ident.C--(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-C.ident.C--(CH.sub.2).sub.t --,CH.sub.2.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.3-7 cycloalkyl-CH.dbd.CH--(CH.sub.2).sub.t --,aryl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-CH.dbd.CH--(CH.sub.2).sub.t --,C.sub.1-6 alkyl-SO.sub.2 --(CH.sub.2).sub.t --,C.sub.1-6 alkylaryl-SO.sub.2 --(CH.sub.2).sub.t --,C.sub.1-8 alkylcarbonylamino,aryl C.sub.1-5 alkoxy,C.sub.1-5 alkoxycarbonyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl,C.sub.1-6 alkylcarbonyloxy,(C.sub.1-6 alkyl).sub.p amino,aminocarbonyl C.sub.1-6 alkyl,C.sub.1-6 alkoxy,aryl C.sub.1-6 alkoxy,(aryl).sub.p amino,(aryl).sub.p amino C.sub.1-6 alkyl,(aryl C.sub.1-6 alkyl).sub.p amino,(aryl C.sub.1-6 alkyl).sub.p amino C.sub.1-6 alkyl,arylcarbonyloxy,aryl C.sub.1-6 alkylcarbonyloxy,(C.sub.1-6 alkyl).sub.p aminocarbonyloxy,C.sub.1-8 alkylsulfonylamino,arylsulfonylamino,C.sub.1-8 alkylsulfonylamino C.sub.1-6 alkyl,arylsulfonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylsulfonylamino,aryl C.sub.1-6 alkylsulfonylamino C.sub.1-6 akyl,C.sub.1-8 alkoxycarbonylamino,C.sub.1-8 alkoxycarbonylamino C.sub.1-8 alkyl,aryloxycarbonylamino C.sub.1-8 alkyl,aryl C.sub.1-8 alkoxycarbonylamino,aryl C.sub.1-8 alkoxycarbonylamino C.sub.1-8 alkyl,C.sub.1-8 alkylcarbonylamino,C.sub.1-8 alkylcarbonylamino C.sub.1-6 alkyl,arylcarbonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylcarbonylamino,aryl C.sub.1-6 alkylcarbonylamino C.sub.1-6 alkyl,aminocarbonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminocarbonylamino,(C.sub.1-8 alkyl).sub.p aminocarbonylamino C.sub.1-6 alkyl,(aryl).sub.p aminocarbonylamino C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminocarbonylamino,(aryl C.sub.1-8 alkyl).sub.p aminocarbonylamino C.sub.1-6 alkyl,aminosulfonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminosulfonylamino,(C.sub.1-8 alkyl).sub.p aminosulfonylamino C.sub.1-6 alkyl,(aryl).sub.p aminosulfonylamino C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminosulfonylamino,(aryl C.sub.1-8 alkyl).sub.p aminosulfonylamino C.sub.1-6 alkyl,C.sub.1-6 alkylsulfonyl,C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,arylsulfonyl C.sub.1-6 alkyl,aryl C.sub.1-6 alkylsulfonyl,aryl C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,C.sub.1-6 alkylcarbonyl,C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,arylcarbonyl C.sub.1-6 alkyl,aryl C.sub.1-6 alkylcarbonyl,aryl C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,C.sub.1-6 alkylthiocarbonylamino,C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,arylthiocarbonylamino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylthiocarbonylamino,aryl C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,(C.sub.1-8 alkyl).sub.p aminocarbonyl C.sub.1-6 alkyl,(aryl).sub.p aminocarbonyl C.sub.1-6 alkyl,(aryl C.sub.1-8 alkyl).sub.p aminocarbonyl, and(aryl C.sub.1-8 alkyl).sub.p aminocarbonyl C.sub.1-6 alkyl;wherein any of the alkyl groups of R.sup.10, R.sup.11, and R.sup.12 are either unsubstituted or substituted with one to three R.sup.1 substituents;whereineach m is independently an integer from 0 to 6;each n is independently an integer from 0 to 6each p is independently an integer from 0 to 2;each r is independently an integer from 1 to 3;each s is independently an integer from 0 to 3;each t is independently an integer from 0 to 3; andv is independently an integer from 0 to 6;provided that one of R.sup.5, R.sup.6, R.sup.7, and R.sup.8 is aryl;and the pharmaceutically acceptable salts thereof.