Triazolyl and tetrazolyl phenyl substituted carbapenems, compositions containing such compounds and methods of use

A triazolyl or tetrazolyl phenyl substituted carbapenem represented by formula I ##STR196## or a pharmaceutically acceptable salt thereof, wherein:

• R.sup.1 and R.sup.2 independently represent H, CH.sub.3 --, CH.sub.3 CH.sub.2 --, (CH.sub.3).sub.2 CH--, HOCH.sub.2 --, CH.sub.3 CH(OH)--, (CH.sub.3).sub.2 C(OH)--, FCH.sub.2 CH(OH)--, F.sub.2 CHCH(OH)--, F.sub.3 CCH(OH)--, CH.sub.3 CH(F)--, CH.sub.3 CF.sub.2 -- or (CH.sub.3).sub.2 CF--;
• R.sup.3 is H or methyl:
• R.sup.a is H or is selected from the group consisting of
• a) --CF.sub.3 ;
• b) a halogen atom selected from the group consisting of:
• --Br, --Cl, --F and --I;
• c) --OH;
• d) --OC1-4 alkyl, wherein the alkyl is optionally mono-substituted by Rq, where Rq is selected from the group consisting of --OH, --OCH.sub.3, --COOM, with M representing H, a negative charge, a metal cation or an ester forming group;
• e) --NR'R" wherein R' and R" independently represent H or C1-4 alkyl;
• f) --S(O).sub.n --R.sup.s, where n=0-2, and R.sup.s is C1-4 alkyl or phenyl, each of which is optionally mono-substituted by R.sup.q as defined above;
• g) --CN;
• h) --C(O)H or --CH(OCH.sub.3).sub.2 ;
• i) --C(O)R.sup.s, where R.sup.s is as defined above;
• j) --C(O)OC1-4 alkyl, where the alkyl is optionally mono-substituted by R.sup.q as defined above;
• k) --C(O)N(R.sup.y)R.sup.z, where R.sup.y and R.sup.z are independently H, C1-4 alkyl, (optionally mono-substituted by R.sup.q as defined above), or N(R.sup.y)R.sup.z are taken together to represent an amino acid residue, or are taken together to represent a 4- to 5-membered alkylidene radical which forms a ring (optionally substituted with R.sup.q as defined above), or a 3- to 4-membered alkylidene radical interrupted by --O--, --S--, --S(O)-- or --S(O).sub.2 --which forms a ring;
• l) --C(S)N(R.sup.y)R.sup.z where R.sup.y and R.sup.z are as defined above:
• m) --SCN;
• n) --SCF.sub.3 ;
• o) --OCF.sub.3 ;
• p) tetrazolyl, where the point of attachment is the carbon atom of the tetrazole ring and one of the nitrogen atoms is mono-substituted by hydrogen, an alkali metal or a C1-C4 alkyl;
• q) a C2-C.sub.4 alkenyl radical, optionally mono-substituted by one of the substituents a) to p) above and phenyl which is optionally substituted by R.sup.q as defined above:
• r) a C2-C4 alkynyl radical, optionally mono-substituted by one of the substituents a) to q) above;
• s) a C1-C4 alkyl radical;
• t) a C1-C4 alkyl group substituted with 1-3 groups R.sup.q as defined above, or mono-substituted by one of the substituents a)-s) above;
• R.sup.b is present or absent;
• when R.sup.b is absent, the nitrogen to which said group is shown optionally attached is uncharged;
• when R.sup.b is present, R.sup.b is selected from the group consisting of:
• (a) --C.sub.1-4 alkyl;
• (b) --NR'R" with R' and R" equal to H or C.sub.1-4 alkyl and (c) C.sub.1-4 alkyl substituted with up to three groups selected from:
• hydroxy;
• C1-4 alkoxy;
• phenyl, nitrophenyl, methoxyphenyl or dimethoxyphenyl;
• heteroaryl;
• heteroaryl substituted with R.sup.s, as defined above;
• --NR'R", with R' and R" as defined above;
• --OC(O)R.sup.s, where R.sup.s is C.sub.1-4 alkyl or phenyl, each of which is optionally mono-substituted by R.sup.q as defined above;
• --C(O)--R.sup.s with R.sup.s as previously defined;
• --C(O)N(R.sup.y)R.sup.z, where R.sup.y and R.sup.z are as defined above;
• --C(O)OC.sub.1-4 alkyl, where the alkyl is optionally mono-substituted by R.sup.q as defined above;
• and
• COOM, with M as defined above;
• one or two of X, Y and Z represent a N atom and the other variables are carbon atoms;
• each R.sup.c is independently selected from the group consisting of hydrogen, halo, C1-4 alkyl, --COOM with M as previously defined, and C1-4 alkyl substituted with from 1 to 3 groups selected from:
• hydroxy;
• --C(O)--Rs with Rs as previously defined;
• COOM, with M as previously defined;
• --O--(C1-4) alkyl, wherein the alkyl portion is optionally substituted with Rq, as defined above;
• --NR'R", with R' and R" as defined above;
• --C(O)O(C1-4) alkyl, where the alkyl portion is optionally mono-substituted with Rq as defined above;
• --C(O)N(R.sup.y)R.sup.z, where R.sup.y and R.sup.z are independently H, C1-4 alkyl (optionally mono-substituted by R.sup.q as defined above), or N(R.sup.y)R.sup.z are taken together to represent an amino acid residue, or are taken together to represent a 4- to 5-membered alkylidene radical which forms a ring (optionally substituted with R.sup.q as defined above), or a 3- to 4-membered alkylidene radical interrupted by --O--, --S--, --S(O)-- or --S(O).sub.2 -- which forms a ring;
• --OC(O)N(R.sup.y)R.sup.z, where R.sup.y and R.sup.z are as defined above:
• alternatively, the two R.sup.c groups may be taken in combination to represent an aromatic ring fused to the ring to which they are attached, said aromatic 5-6 membered ring selected from the group consisting of phenyl, pyridine, pyrazine, pyrimidine, pyrrole, imidazole, thiophene, furan and thiazole;
• W is selected from:
• --COOH, or a pharmaceutically acceptable salt or ester thereof;
• COORP where RP is a readily removable carboxyl covering group which is not a pharmaceutically acceptable ester;
• COOM.sup.a where M.sup.a is an alkali metal, or a negative charge.