Patent ID: 6310055
Filing Date: 2001-10-30
Classification: A61P,C07D

Abstract:
A compound represented by formula I: ##STR62##or a pharmaceutically acceptable salt thereof, wherein:R.sup.1 represents H or methyl;CO.sub.2 M represents a carboxylic acid, a carboxylate anion, or a pharmaceutically acceptable ester group, provided that when CO.sub.2 M represents a carboxylate anion it is balanced by Q;X represents a halogen selected from the group consisting of iodine, bromine, chlorine or fluorine;P represents hydrogen, hydroxyl, or F;Z represents trans-ethenediyl or ethynediyl;each R is independently selected from: --R*; --Q; hydrogen; halo; --CN; --NO.sub.2 ; --NR.sup.a R.sup.b ; --OR.sup.c ; --SR.sup.c ; --C(O)NR.sup.a R.sup.b ; --C(O)OR.sup.h ; --S(O)R.sup.c ; --SO.sub.2 R.sup.c ; --SO.sub.2 NR.sup.a R.sup.b ; --NR.sup.a SO.sub.2 R.sup.b ; --C(O)R.sup.a ; --OC(O)R.sup.a ; --OC(O)NR.sup.a R.sup.b ; --NR.sup.a C(O)NR.sup.b R.sup.c ; --NR.sup.a CO.sub.2 R.sup.h ; --OCO.sub.2 R.sup.h ; --NR.sup.a C(O)R.sup.b ; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.d groups; --C.sub.3-7 cycloalkyl, unsubstituted or substituted with one to four R.sup.d groups and A--(CH.sub.2).sub.n --Q, wherein A is O, S, or CH.sub.2, and n is 0-3;each R.sup.a, R.sup.b and R.sup.c independently represents hydrogen, --R*, --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.d groups, or --C.sub.3-7 cycloalkyl, unsubstituted or substituted with one to four R.sup.d groups;each R.sup.d independently represents halo; --CN; --NO.sub.2 ; --NR.sup.e R.sup.f ; --OR.sup.g ; --SR.sup.g ; --CONR.sup.e R.sup.f ; --COOR.sup.g ; --SOR.sup.g ; --SO.sub.2 R.sup.g ; --SO.sub.2 NR.sup.e R.sup.f ; --NR.sup.e SO.sub.2 R.sup.f ; --COR.sup.e ; --NR.sup.e COR.sup.f ; --OCOR.sup.e ; --OCONR.sup.e R.sup.f ; --NR.sup.e CONR.sup.f R.sup.g ; --NR.sup.e CO.sub.2 R.sup.h ; --OCO.sub.2 R.sup.h ; --C(NR.sup.e)NR.sup.f R.sup.g ; --NR.sup.e C(NH)NR.sup.f R.sup.g ; --NR.sup.e C(NR.sup.f)R.sup.g ; --R* or --Q;R.sup.e, R.sup.f and R.sup.g represent hydrogen; --R*; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups;each R.sup.i independently represents halo; --CN; --NO.sub.2 ; phenyl; --NHSO.sub.2 R.sup.h ; --OR.sup.h, --SR.sup.h ; --N(R.sup.h).sub.2 ; --N.sup.+ (R.sup.h).sub.3 ; --C(O)N(R.sup.h).sub.2 ; --SO.sub.2 N(R.sup.h).sub.2 ; heteroaryl; heteroarylium; --CO.sub.2 R.sup.h ; --C(O)R.sup.h ; --OCOR.sup.h ; NHCOR.sup.h ; guanidinyl; carbamimidoyl or ureido;each R.sup.h independently represents hydrogen, a --C.sub.1-6 straight or branched-chain alkyl group, a --C.sub.3 -C.sub.6 cycloalkyl group or phenyl,Q is selected from the group consisting of: ##STR63##wherein:a and b are 1, 2 or 3;L.sup.- is a pharmaceutically acceptable counterion;.alpha. represents O, S or NR.sup.s ;.beta., .delta., .lambda., .mu. and .sigma. represent CR.sup.t, N or N.sup.+ R.sup.s, provided that no more than one of .beta., .delta., .lambda., .mu. and .sigma. is N.sup.+ R.sup.s ;R* is selected from the group consisting of: ##STR64##wherein:d represents O, S or NR.sup.k ;e, g, x, y and z represent CR.sup.m, N or N.sup.+ R.sup.k, provided that no more than one of e, g, x, y and z in any given structure represents N.sup.+ R.sup.k ;R.sup.k represents hydrogen; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups; or --(CH.sub.2).sub.n Q where n=1, 2 or 3 and Q is as previously defined;each R.sup.m independently represents a member selected from the group consisting of: hydrogen; halo; --CN; --NO.sub.2 ; --NR.sup.n R.sup.o ; --OR.sup.n ; --SR.sup.n ; --CONR.sup.n R.sup.o ; --COOR.sup.h ; --SOR.sup.n ; --SO.sub.2 R.sup.n ; --SO.sub.2 NR.sup.n R.sup.o ; --NR.sup.n SO.sub.2 R.sup.o ; --COR.sup.n ; --NR.sup.n COR.sup.o ; --OCOR.sup.n ; --OCONR.sup.n R.sup.o ; --NR.sup.n CO.sub.2 R.sup.h ; --NR.sup.n CONR.sup.o R.sup.h ; --OCO.sub.2 R.sup.h ; --CNR.sup.n NR.sup.o R.sup.h ; --NR.sup.n CNHNR.sup.o R.sup.h ; --NR.sup.n C(NR.sup.o)R.sup.h ; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups; --C.sub.3-7 cycloalkyl, unsubstituted or substituted with one to four R.sup.i groups; and --(CH.sub.2).sub.n Q where n and Q are as defined above;R.sup.n and R.sup.o represent hydrogen, phenyl; --C.sub.1-6 straight- or branched-chain alkyl unsubstituted or substituted with one to four R.sup.i groups;each R.sup.s independently represents hydrogen; phenyl or --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups;each R.sup.t independently represents hydrogen; halo; phenyl; --CN; --NO.sub.2 ; --NR.sup.u R.sup.v ; --OR.sup.u ; --SR.sup.u ; --CONR.sup.u R.sup.v ; --COOR.sup.h ; --SOR.sup.u ; --SO.sub.2 R.sup.u ; --SO.sub.2 NR.sup.u R.sup.v ; --NR.sup.u SO.sub.2 R.sup.v ; --COR.sup.u ; --NR.sup.u COR.sup.v ; --OCOR.sup.u ; --OCONR.sup.u R.sup.v ; --NR.sup.u CO.sub.2 R.sup.v ; --NR.sup.u CONR.sup.v R.sup.w ; --OCO.sub.2 R.sup.v ; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups;R.sup.u and R.sup.v represent hydrogen or --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups;each R.sup.w independently represents hydrogen; --C.sub.1-6 straight- or branched-chain alkyl, unsubstituted or substituted with one to four R.sup.i groups; C.sub.3-6 cycloalkyl optionally substituted with one to four R.sup.i groups; phenyl optionally substituted with one to four R.sup.i groups, or heteroaryl optionally substituted with 1-4 R.sup.i groups;R.sup.x represents hydrogen or a C.sub.1-8 straight- or branched-chain alkyl, optionally interrupted by one or two of O, S, SO, SO.sub.2, NRW, N.sup.+ R.sup.h R.sup.w, or --C(O)--, said chain being unsubstituted or substituted with one to four of halo, CN, NO.sub.2, OR.sup.w, SR.sup.w, SOR.sup.w, SO.sub.2 R.sup.w, NR.sup.h R.sup.w, N.sup.+ (R.sup.h).sub.2 R.sup.w, --C(O)--R.sup.w, C(O)NR.sup.h R.sup.w, SO.sub.2 NR.sup.h R.sup.w, CO.sub.2 R.sup.w, OC(O)R.sup.w, OC(O)NR.sup.h R.sup.w, NR.sup.h C(O)R.sup.w, NR.sup.h C(O)NR.sup.h R.sup.w, or a phenyl or heteroaryl group which is in turn optionally substituted with from one to four Ri groups or with one to two C.sub.1-3 straight- or branched-chain alkyl groups, said alkyl groups being unsubstituted or substituted with one to four Ri groups; andR.sup.y and R.sup.z represent hydrogen; phenyl; --C.sub.1-6 straight or branched chain alkyl, unsubstituted or substituted with one to four R.sup.i groups, and optionally interrupted by O, S, NR.sup.w, N.sup.+ R.sup.h R.sup.w or --C(O)--;Wherein the molecule contains no more than two cations balanced by a carboxylate anion and a negatively charged pharmaceutically acceptable counterion.