Patent ID: 6255496
Filing Date: 2001-07-03
Classification: A61P,C07C,C07D,C07F

Abstract:
A compound of the formula ##STR254##wherein W is CH.dbd.CH, CH.dbd.N, O or S;R.sup.1 is (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylthio, halo, hydroxy, cyano, ##STR255##in which R.sup.2 and R.sup.3 are each independently hydrogen or (C.sub.1 -C.sub.6)alkyl, --COO--(C.sub.1 -C.sub.6)alkyl, CF.sub.3, (C.sub.1 -C.sub.6)alkylphenyl, phenyl or phenyl substituted by one or more of (C.sub.1 -C.sub.6)alkyl, --COO--(C.sub.1 -C.sub.6)alkyl, ##STR256##in which R.sup.2 and R.sup.3 are as defined above, halo, hydroxy, --O--(C.sub.1 -C.sub.6)alkyl, --S--(C.sub.1 -C.sub.6)alkyl or (C.sub.2 -C.sub.6)alkenyl;p is 0,1 or 2;A is V--(R.sup.c).sub.n --;R.sup.c is a straight or branched chain alkyl group;n is 0 or an integer of from 1 to 6;R.sup.a and R.sup.b when taken together form an oxo group; or R.sup.a and R.sup.b are each independently hydrogen or OH;V is O, --S--, --SO--, --SO.sub.2, --CONH or NHCO when n is an integer of from 1 to 6 or V is (C.sub.2 -C.sub.6)alkenyl or a bond when n is 0 or an integer of from 1 to 6;D is --(CH.sub.2).sub.m or a bond linking ##STR257##ring to Y;m is an integer of from 1 to 6;Y is --O--, --S--, --SO--, --SO.sub.2, ##STR258##or a bond;R.sup.4 is as defined below for R.sup.7 ;Z is: ##STR259##in which B is: ##STR260##--SO.sub.2 -- or a bond;X is S or O;q is an integer from 1 to 6;R.sup.9 is hydrogen or (C.sub.1 -C.sub.6)alkyl;R.sup.10 is hydrogen, CN, NO.sub.2, OH, --O--(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl, phenyl or (C.sub.1 -C.sub.6)alkylphenyl;R.sup.5 and R.sup.6 are each independently hydrogen or (C.sub.1 -C.sub.18)alkyl;R.sup.7 and R.sup.8 are each independently;(a) hydrogen;(b) (C.sub.1 -C.sub.18)alkyl;(c) (C.sub.1 -C.sub.18)alkyl substituted by one or more of(1) phenyl;(2) phenyl substituted by 1-5 fluoro, 1-3 halo (other than fluoro), 1-3(C.sub.1 -C.sub.6)alkoxy, 1-3(C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkylthio, amino, 1-3 (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, --CO.sub.2 H, --COO--(C.sub.1 -C.sub.6)alkyl, --SO.sub.3 H, --SO.sub.2 NHR.sup.15 in which R.sup.15 is hydrogen or (C.sub.1 -C.sub.6)alkyl or ##STR261##in which R.sup.2 and R.sup.3 are as defined above;(3) heterocyclic selected from oxadiazolyl, isoxazolyl, oxazolyl, furyl and thiazolyl;(4) heterocyclic substituted by one or more of phenyl, phenyl substituted by 1-3 halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkylthio, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, CO.sub.2 H, --COO--(C.sub.1 -C.sub.6)alkyl, --SO.sub.3 H, SO.sub.2 NHR.sup.15 in which R.sup.15 is hydrogen or (C.sub.1 -C.sub.6)alkyl, or ##STR262##in which R.sup.2 and R.sup.3 are as defined above, (C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkyl substituted by one or more phenyl or heterocyclic groups, said phenyl or heterocyclic group being unsubstituted or substituted by 1-3 halo, 1-3 (C.sub.1 -C.sub.6)alkoxy, 1-3 (C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkylthio, amino, 1-3 (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, COOH, --COO--(C.sub.1 -C.sub.6)alkyl, --SO.sub.3 H, --SO.sub.2 NHR.sup.15 in which R.sup.15 is hydrogen or ((C.sub.1 -C.sub.6)alkyl, or ##STR263##in which R.sup.2 and R.sup.3 are each independently hydrogen or (C.sub.1 -C.sub.6)alkyl, the heterocyclic radical being selected from imidazolyl, oxadiazolyl, isoxazolyl, pyrrolyl, pyrazolyl, oxazolyl, furyl, thianyl or thiazolyl;(5) carboxy or --COO--(C.sub.1 -C.sub.6)alkyl;(6) hydroxy, halo, --O--(C.sub.1 -C.sub.6)alkyl or --S--(C.sub.1 -C.sub.6)alkyl, with the proviso that the OH, ethers or thioethers cannot be on the carbon bearing the heteroatoms;(7) cyano;(8) halogen, trifluoromethyl or trifluoroacetyl;(9) CH.sub.2 L-R.sup.16 in which L is ##STR264##or --O--SiR.sup.16 R.sup.18 R.sup.19 or a bond in which R.sup.16 and R.sup.17 are each independently (C.sub.1 -C.sub.18)alkyl or (C.sub.2 -C.sub.18)alkenyl or (C.sub.1 -C.sub.18)alkyl or (C.sub.2 -C.sub.18)alkenyl substituted by one or more phenyl or heterocyclic radicals, said phenyl or heterocyclic radicals being unsubstituted or substituted by 1-5 fluoro, 1-3 halo (other than fluoro), 1-3 (C.sub.1 -C.sub.6)alkoxy, 1-3(C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, 1-3 trifluoromethyl, 1-3 (C.sub.1 -C.sub.6)alkylthio, amino, 1-3(C.sub.1 -C.sub.6)alkylamino, 1-3 di(C.sub.1 -C.sub.6)alkylamino, CO.sub.2 H, 1-3 --COO(C.sub.1 -C.sub.6)alkyl, ##STR265##or --SO.sub.2 NHR.sup.9 in which R.sup.9 is hydrogen or ((C.sub.1 -C.sub.6)alkyl and R.sup.2 and R.sup.3 are as defined above; ##STR266##in which B.sup.1 is ##STR267##--SO.sub.2 --, --PO(OR.sup.9).sub.2 or a bond; providing that when B.sup.1 is --PO(OR.sup.9).sub.2, then R.sup.7 becomes R.sup.9, and when B.sup.1 is ##STR268##or --SO.sub.2 --, then R.sup.7 cannot be hydrogen;X, q, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are as defined in (a); ##STR269##in which q, R.sup.5 and R.sup.6 are as defined above;R.sup.18, R.sup.19 and R.sup.11 are as defined below for R.sup.7 and R.sup.8 except that they may not be hydrogen, or R.sup.18 and R.sup.19 taken together with the nitrogen to which they are attached represent a 4, 5- or 6-membered heterocyclic ring and Y, R.sup.7 and R.sup.11 are as defined above, or R.sup.18, R.sup.19 and R.sup.11 taken together with the nitrogen to which they are attached represent pyridinium, said pyridinium group being unsubstituted or substituted by ((C.sub.1 -C.sub.12))alkyl, (C.sub.1 -C.sub.12)alkoxy, amino, (C.sub.1 -C.sub.12)alkylamino, di (C.sub.1 -C.sub.12)alkylamino, ##STR270##--S--(C.sub.1 -C.sub.12)alkyl, ##STR271##in which R.sup.2 and R.sup.3 are as defined above, phenyl or phenyl (C.sub.1 -C.sub.10)alkyl; ##STR272##in which R.sup.13 is (C.sub.1 -C.sub.18)alkyl or (C.sub.1 -C.sub.18)alkyl substituted by carboxy, ##STR273##in which R.sup.2 and R.sup.3 are as defined above, hydroxy, --O--(C.sub.1 -C.sub.6)alkyl or --S--((C.sub.1 -C.sub.6)alkyl substituted by 1 or 2 phenyl or substituted phenyl groups, the substituents for the substituted phenyl groups being 1-5 fluoro or 1-3 halo (other than fluoro), (C.sub.1 -C.sub.6) alkoxy, (C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6) alkylthio, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, CO.sub.2 H, COO--(C.sub.1 -C.sub.6)alkyl, SO.sub.3 H, SO.sub.2 NHR.sup.15 in which R.sup.15 is hydrogen or (C.sub.1 -C.sub.6) alkyl or ##STR274##in which R.sup.2 and R.sup.3 are as defined above;r is 0 or an integer of from 1 to 3;R.sup.7 is as defined above;M is --(CH.sub.2 --).sub.m T where T is ##STR275##in which R.sup.2 is as defined above, --SO.sub.2 -- or a bond when MR.sup.7 is on nitrogen and providing that when T is ##STR276##then R.sup.7 cannot be hydrogen, and T is ##STR277##or a bond whenMR.sup.7 is on a carbon atom of the heterocyclic ring;R.sup.14 is hydrogen or (C.sub.1 -C.sub.6)alkyl;m is 0 or an integer of 1-6; ##STR278##wherein Q is --O--, --S--, --SO-- or --SO.sub.2 --, and q, R.sup.5, R.sup.6 and R.sup.7 are as defined above, providing that when Q is --SO-- or --SO.sub.2 --, R.sup.7 cannot be hydrogen;f) R.sup.7 wherein R.sup.7 is defined above, providing that when Y is --SO-- or --SO.sub.2 --, R.sup.7 cannot be hydrogen; andR.sup.18 and R.sup.19 are phenyl or phenyl substituted by 1-3 halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkyl, nitro, cyano, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkylthio, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6) alkylamino, CO.sub.2 H, --COO--(C.sub.1 -C.sub.6)alkyl, --SO.sub.3 H, SO.sub.2 NHR.sup.15 in which R.sup.15 is hydrogen or (C.sub.1 -C.sub.6)alkyl, or ##STR279##in which R.sup.2 and R.sup.3 are as defined above; or a pharmaceutically acceptable salt, or solvate thereof.