Patent ID: 6017935
Filing Date: 2000-01-25
Classification: C07D

Abstract:
A compound of formula I, or a pharmaceutically acceptable salt thereof ##STR38## wherein R is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, or --Z.sup.1 --R.sup.3 ;Z.sup.1 is a direct bond, C.sub.1-6 alkyl, or --O-C.sub.1-6 alkyl;R.sup.3 is aryl, substituted aryl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, cyclic 3-7 membered ring consisting of either one or two heteroatoms, or heteroaryl;R.sup.A is --NHC(O)R, --NHC(O)OR, --NHC(O)NHR, --NHC(O)N(R).sub.2, --NHS(O).sub.k R, --NHP(.dbd.O)(OR).sub.2 or --NHP.dbd.S(OR).sub.2, where k is 1 or 2;R.sup.B is hydroxy, fluoro, --OC(OR)R.sup.x, --OC(O)OR.sup.x, OP(O)(OH).sub.2, OCH.sub.2 OP(O)(OH).sub.2, --OCH.sub.2 OCH.sub.2 OP(.dbd.O)(OH).sub.2, --(OCH).sub.2).sub.m OC.dbd.OCH.sub.2 NHR.sup.x, --(OCH.sub.2).sub.m OC(.dbd.O)CH(R"")NR'.sub.6 R'.sub.7 where m is 0-3, --OCOCH.sub.2 CH.sub.2 NH.sub.3.sup.+ HCOO.sup.-, --OCOCH.sub.2 CH.sub.2 COOH, --OCO(CH.sub.2).sub.3 COOH,--OC(O)(CH.sub.2).sub.n NR.sup.F R.sup.G, where n is 0-3, --OC(O)CH.sub.2 CH.sub.2 C(O)OCH.sub.2 CH.sub.2 OH or --OC(O)--Z--C(O)--R'; Z is ethylene (--CH.sub.2 CH.sub.2 --), propylene (--CH.sub.2 CH.sub.2 CH.sub.2 --), --CH.dbd.CH--, 1,2-cyclohexane or 1,2-phenylene;R' is --OH, --NR'.sub.2 R'.sub.3, --OR'.sub.3, --SR'.sub.3, or --OCH.sub.2 C(O)NR'.sub.4 R'.sub.5 ;R'.sub.2 is --H or --CH.sub.3 ;R'.sub.3 is --(CH.sub.2).sub.j NR'.sub.6 R'.sub.7 or (CH.sub.2).sub.n N.sup.+ R'.sub.6 R'.sub.7 R'.sub.8 X.sup.-, where j is 1-3;R'.sub.4 is --H or --C.sub.1 -C.sub.4 alkyl;R'.sub.5 is --H, --C.sub.1 -C.sub.4 alkyl, benzyl, hydroxyethyl, --CH.sub.2 CO.sub.2 H or dimethylaminoethyl;R'.sub.6 and R'.sub.7 are independently --H, --CH.sub.3, --CH.sub.2 CH.sub.3, benzyl or R'.sub.6 and R'.sub.7 together with the nitrogen of NR'.sub.6 R'.sub.7 form a pyrrolidino, piperidino, morpholino, or N-methylpiperizino group;R'.sub.8 is --CH.sub.3, --CH.sub.2 CH.sub.3 or benzyl;X.sup.- is halide;R.sup.F and R.sup.G are independently --H or --C.sub.1 -C.sub.3 alkyl, or R.sup.F and R.sup.G taken together with the nitrogen of NR.sup.F R.sup.G form a pyrrolidino, piperidino, morpholino or N-methylpiperizino groups;R"" is --H, --CH.sub.3, --CH.sub.2 CH(CH.sub.3).sub.2, --CH(CH.sub.3)CH.sub.2 CH.sub.3, --CH(CH.sub.3).sub.2, --CH.sub.2 phenyl, --(CH.sub.2).sub.3 NH.sub.2, --(CH.sub.2).sub.4 NH.sub.2, --CH.sub.2 CH.sub.2 COOH, --(CH.sub.2).sub.3 NHC(.dbd.NH)NH.sub.2, the residue of the amino acid proline, --OC(O)CH.dbd.CH.sub.2, --C(O)CH.sub.2 CH.sub.2 C(O)NHCH.sub.2 CH.sub.2 SO.sub.3 --Y+ or --OC(O)CH.sub.2 CH.sub.2 C(O)NHCH.sub.2 CH.sub.2 CH.sub.2 SO.sub.3 --Y+;Y+ is Na+ or N+(Bu).sub.4 ;R.sup.2 is aryl or substituted aryl;R.sup.4 is --C.sub.1-6 alkyl, --OC--C.sub.1-6 alkyl, or --C.sub.3-6 cycloalkyl;R.sup.6 and R.sup.6' are independently hydrogen, hydroxy, C.sub.1-6 alkyl, --SH, --S--R.sup.W, halo, or together R.sup.6 and R.sup.6' form a ketone;R.sup.7 and R.sup.7' are independently hydrogen, mercapto, --S--R.sup.W, --S(R.sup.W).sub.2.sup.+ K.sup.-, --S(O)--R.sup.W, --S(O).sub.2 R.sup.W, --S(O).sub.2 OH and the corresponding salts, --S(O).sub.2 NHR.sup.x, --S(O).sub.2 N(R.sup.x).sub.2, --S--S--R.sup.W, --S--S--R.sup.3, --S(CH.sub.2).sub.a R.sup.3, where a is 0-4, --S--CN, --S(O)--CN, --S(O).sub.2 --CN, --SC(O)R.sup.x, --SC(O)OR.sup.x, --SC(S)R.sup.x, --SC(S)SR.sup.x, --SC(O)NHR.sup.x, --SC(OH)NR'.sub.6 R'.sub.7, --SCH.sub.2 OR, --SC(R.sup.x).sub.2 OR, --SCHR.sup.x OR, --SCH.sub.2 OCH.sub.2 OCH.sub.3, --SCH.sub.2 SR, --SC(R.sup.x).sub.2 SR, --SCHR.sup.x SR, --SCOCH.sub.2 CH.sub.2 NH.sub.3.sup.+ HCOO.sup.-, --SCOCH.sub.2 CH.sub.2 COOH, --SCO(CH.sub.2).sub.3 COOH, OC(O)(CH.sub.2).sub.n NR.sup.F R.sup.G, where n is 0-3, with the proviso that n is not 1 when R.sup.F and R.sup.G are each methyl, --SC(O)--Z--C(O)--R', --SC(O)CH.sub.2 CH.sub.2 C(O)OCH.sub.2 CH.sub.2 OH, --S(O).sub.b CH.sub.2 CN, where is b is 0-2, --SCH.sub.2 C(O)C.sub.1-6 alkyl, --SCH.dbd.C(X)(Y), --S(SCH.sub.2).sub.r R.sup.2, where r is 1-4, or --S(CH.sub.2)S(O).sub.t C.sub.1-6 alkyl, where t is 0-2, with the proviso that both of R.sup.7 and R.sup.7' cannot simultaneously be hydrogen;X and Y are independently hydrogen, COOR.sup.a, C(O)R.sup.a, R.sup.a, CN, aryl or heteroaryl, where R.sup.a is C.sub.1-6 alkyl;K is Br.sup.-, Cl.sup.-, I.sup.-, CH.sub.3 SO.sub.3 --, BF.sub.4 --, CF.sub.3 COO--, CH.sub.3 COO-- or CF.sub.3 SO.sub.2 --;R.sup.9 and R.sup.9' are independently hydrogen or hydroxy or together R.sup.9 and R.sup.9' form a ketone; provided R.sup.9' and R.sup.7' taken together can form part of a ring joined by --CH.sub.2 S(O).sub.q -- in which the carbon is attached at R.sup.9' and the sulfur at R.sup.7' and where q is 0-2, R.sup.9 is --OH, and R.sup.7 is hydrogen; further provided R.sup.9' and R.sup.7' taken together can form part of a ring joined by .dbd.CHS(O).sub.q -- in which the carbon is attached at R.sup.9 and R.sup.9' to form a double bond and the sulfur at R.sup.7' and where q is 0-2, and R.sup.7 is hydrogen;R.sup.10 is hydrogen, hydroxy, --OC(O)R.sup.x, --OC(O)OR.sup.x, --O--C.sub.1-6 alkyl, --OCH.sub.2 OCH.sub.3, --OCH.sub.2 OCH.sub.2 OCH.sub.3, --OCH.sub.2 OCH.sub.2 OCH.sub.2 CH.sub.3, --OCH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 --OCH.sub.2 OCH.sub.2 CH.sub.2 OH, --OCH.sub.2 SR, --OCH.sub.2 OCH.sub.2 SCH.sub.3, --OC(O)NR'.sub.6 R'.sub.7, C.sub.1-6 alkyl, --(CH.sub.2).sub.3 C(O)R.sup.x, --(CH.sub.2).sub.3 C(O)OR.sup.x, --(CH.sub.2).sub.3 CN, --OP(O)(OH).sub.2, --OCH.sub.2 OP(O)(OH.sub.2), --OCH.sub.2 OCH.sub.2 OP(O)(OH.sub.2, --(OCH.sub.2).sub.n OC.dbd.OCH.sub.2 NHR.sup.x, --(OCH.sub.2).sub.n OC(.dbd.O)CH.sub.(R"")NR'.sub.6 R'.sub.7, where n is 0-3, --OCOCH.sub.2 CH.sub.2 NH.sub.3.sup.+ HCOO.sup.+, --OCOCH.sub.2 CH.sub.2 COOH, --OCO(CH.sub.2).sub.3 COOH, --OC(O)--Z--C(O)--R', --OC(O)(CH.sub.2).sub.n NR.sup.F R.sup.G where n is 0-3, or --OC(O)CH.sub.2 CH.sub.2 C(O)OCH.sub.2 CH.sub.2 OH;R.sup.19 is methyl or hydroxymethyl;R.sup.X is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cyclo alkyl any of which groups can be optionally substituted with one to six of the same or different halogen atoms or with one or more hydroxy groups; andR.sup.W is C.sub.1-6 alkyl any of which groups can be optionally substituted with one to six of the same or different halogen atoms or with one or more hydroxy groups or with one or more carboxy groups or with one or more carboxy C.sub.1-6 alkyl esters or with one or more mercapto groups.