Carbapenems and 1-methylcarbapenems having an externally alkylated mono- or bicyclic 2-quaternary heteroarylalkyl substituent

Claim 1

A compound having the formula: ##STR135## wherein: R 1 is hydrogen or methyl; R 4 and R 5 are independently H, CH 3 --, CH 3 CH 2 --, (CH 3 ) 2 CH--, HOCH 2 --, CH 3 CH(OH)--, (CH 3 ) 2 C(OH)--, FCH 2 --, F 2 CH--, F 3 C--, CH 3 CH(F)--, (CH 3 ) 2 C(F)--; CH 3 CF 2 --, or L is a bridging group comprising substituted or unsubstituted C 1 -C 4 straight, C 2 -C 6 branched or C 3 -C 7 cycloalkyl groups wherein the substituents are selected from C 1 -C 6 alkyl, O-C 1 -C 6 alkyl, S-C 1 -C 6 alkyl, CF 3 , N(C 1 -C 6 alkyl) 2 ; ##STR136## is a mono- or bicyclic heteroarylium group containing from 5-11 ring atoms of which up to 5 are heteroatoms in addition to the quaternary nitrogen; wherein: R 2 is (1) an unsubstituted or substituted C 1 -C 6 alkyl radical; (2) an unsubstituted or substituted C 2 -C 6 alkenyl radical; (3) an unsubstituted or substituted C 2 -C 6 alkynyl radical; (4) a C 3 -C 7 cycloalkyl radical in which the ring is substituted or unsubstituted and one or more atoms may be replaced by a heteroatom; (5) a C 3 -C 7 cycloalkyl methyl radical in which the ring may be substituted and one or more atoms may be replaced by a heteroatom; (6) an unsubstituted or substituted C 5 -C 7 cycloalkenyl radical; (7) an unsubstituted or substituted bivalent C 2 -C 6 alkylidene radical, optionally interrupted by a heteroatom, and joined to the heteroarylium group to form a ring which is carbocyclic or in which one or more atoms is replaced by a heteroatom and wherein the new ring may contain one or more double bonds; (8) an unsubstituted or substituted phenyl or heteroaryl radical; (9) an unsubstituted or substituted phenyl (C 1 -C 4 alkyl) or heteroaryl (C 1 -C 4 alkyl) radical; (10) a cyano (C 1 -C 4 alkyl) radical; (11) a carboxy (C 1 -C 4 alkyl) radical; (12) a sulfo (C 1 -C 4 alkyl) radical; (13) a carbamoyl (C 1 -C 4 alkyl) radical; (14) a phosphonyl (C 1 -C 4 alkyl) radical; (15) a hydroxy (C 1 -C 4 alkyl) radical; or (16) an amino (C 1 -C 4 alkyl) radical in which the nitrogen atom is unsubstituted or substituted with one to three C 1 -C 4 alkyl groups; wherein the substituents in the above definitions of R 2 are independently selected from the group consisting of: (a) a trifluoromethyl group; (b) a halogen atom; (c) an unsubstituted or substituted C 1 -C 4 alkoxyl radical; (d) a hydroxy group; (e) an unsubstituted or substituted (C 1 -C 6 alkyl) carbonyloxy radical; (f) a carbamoyloxy radical which is unsubstituted or substituted on nitrogen with one or two C 1 -C 4 alkyl groups; (g) a C 1 -C 6 alkylthio radical, C 1 -C 6 alkylsulfinyl radical or C 1 -C 6 alkylsulfonyl radical, each of which is unsubstituted or substituted on the alkyl group; (h) a sulfo group; (i) a sulfamoyl group which is unsubstituted or substituted on nitrogen by one or two C 1 -C 4 alkyl groups; (j) a formylamino group; (k) an unsubstituted or substituted (C 1 -C 6 alkyl)carbonylamino radical; (l) a (C 1 -C 4 alkoxyl) carbonylamino radical; (m) a ureido group in which the terminal nitrogen is unsubstituted or substituted with one or two C 1 -C 4 alkyl groups; (n) an arylsulfonamido or a (C 1 -C 6 alkyl)sulfonamido group; (o) a cyano group; (p) a formyl or acetalized formyl radical; (q) an unsubstituted or substituted (C 1 -C 6 alkyl)carbonyl radical wherein the carbonyl is free or acetalized; (r) an unsubstituted or substituted phenylcarbonyl or heteroarylcarbonyl radical; (s) a carboxyl group; (t) a (C 1 -C 6 alkoxy)carbonyl radical; (u) a carbamoyl radical which is unsubstituted or substituted on nitrogen by one or two C 1 -C 4 alkyl groups; (v) an N-hydroxycarbamoyl or N(C 1 -C 4 alkoxy)carbamoyl radical in which the nitrogen atom may be additionally substituted by a C 1 -C 4 alkyl group; (w) a thiocarbamoyl group; (x) a 5-(1H)-tetrazolyl group; (y) a phosphonate group --P(O) (OH)OR' where R' is C 1 -C 3 alkyl; (z) an alkyl phosphonate group --(CH 2 ) n P(O) (OH) (OR') where n=1 to 3 and R' is C 1 -C 3 alkyl; (aa) hydrogen; (ab) an unsubstituted or substituted C 1 -C 6 alkyl radical; (ac) an unsubstituted or substituted C 2 -C 6 alkenyl radical; (ad) an unsubstituted or substituted C 2 -C 6 alkynyl radical; (ae) a C 3 -C 7 cycloalkyl radical in which the ring is substituted or unsubstituted and one or more atoms may be replaced by a heteroatom; (af) a C 3 -C 7 cycloalkyl methyl radical in which the ring may be substituted and one or more atoms may be replaced by a heteroatom; (ag) an unsubstituted or substituted C 5 -C 7 cycloalkenyl radical; (ah) an unsubstituted or substituted phenyl or heteroaryl radical; and (ai) an unsubstituted or substituted phenyl (C 1 -C 4 alkyl) or heteroaryl (C 1 -C 4 alkyl) radical; and R 3 is (a) hydrogen; (b) an unsubstituted or substituted C 1 -C 6 alkyl radical; (c) an unsubstituted or substituted C 2 -C 6 alkenyl radical; (d) an unsubstituted or substituted C 2 -C 6 alkynyl radical; (e) a C 3 -C 7 cycloalkyl radical in which the ring is substituted or unsubstituted and one or more atoms may be replaced by a heteroatom; (f) a C 3 -C 7 cycloalkyl methyl radical in which the ring may be substituted and one or more atoms may be replaced by a heteroatom; (g) an unsubstituted or substituted C 5 -C 7 cycloalkenyl radical; (h) an unsubstituted or substituted phenyl or heteroaryl radical; (i) an unsubstituted or substituted phenyl (C 1 -C 4 alkyl) or heteroaryl (C 1 -C 4 alkyl) radical; and (j) a trifluoromethyl group; (k) a halogen atom; (l) an unsubstituted or substituted C 1 -C 4 alkoxyl radical; (m) a C 1 -C 6 alkylthio radical, C 1 -C 6 alkylsulfinyl radical or C 1 -C 6 alkylsulfonyl radical, each of which is unsubstituted or substituted on the alkyl group; (n) a mono (C 1 -C 4 alkyl) amino or di(C 1 -C 4 alkyl)amino group, each of which is unsubstituted or substituted on the alkyl group; or (o) a cyano group; and Y is (i) COOH or a pharmaceutically acceptable ester or salt thereof, (ii) COOR wherein R is a removable carboxy protecting group, (iii) COOM wherein M is an alkali metal, or (iv) COO - ; provided that when Y is other than (iv) a counterion Z - is provided.