PROCESS FOR PRODUCING SUBSTITUTED IN 4-LOCATION ALKYL-CARBAPENEM ANTIBIOTICS AND PHARMACEUTICAL PREPARATIVES CONTAINING SUCH ACTIVE SUBSTANCES

摘要

Compounds of the formula A is an unsubstituted or hydroxy-substituted straight or branched C1-10 alkylene group or a straight or branched C1-10 alkylene group having an intervening heteroatom selected from oxygen, sulfur and nitrogen; R<2> is hydroxy, halogen, C1-4 alkoxy, nitrile, azido, a quaternary ammonio group, -NR<5>R<6>, B is a straight or branched C1-6 alkylene group or a direct bond when R<3> is joined to the sulfur atom through a carbon atom thereof; R<3> is a residue of an organic group; R<4> is hydrogen, a removable carboxy-protecting group or a physiologically hydrolyzable ester group; R<5> and R<6> each are independently hydrogen, C1-6 alkyl, C1-4 alkoxy, hydroxyethyl, azidoethyl, aminoethyl, and when R<5> is hydrogen or C1-4 alkyl, R<6> is hydroxy, C1-4 alkoxy, amino, C1-4 alkylamino, di(C1-4)alkylamino, substituted C1-4 alkyl wherein said alkyl substituent is selected from hydroxy, azido, amino, guanidino, nitrile, carboxy, formimidoyl and phenyl, or an acyl residue of an amino acid or peptide; or R<5> and R<6>, taken together with the nitrogen atom to which they are attached, is an unsubstituted or substituted heterocyclic ring having 1 to 2 ring members and having up to four heteroatoms in each ring independently selected from oxygen, nitrogen and sulfur, wherein said substituent is selected from the group consisting of C1-4 alkyl1 C1-4 alkoxy, trifluoromethyl, hydroxy, halogen, amino, nitrile, carboxy, carbamido, carbamoyl, C1-4 alkylamino and amino (C1-4) alkyl; W is a direct bond, oxygen, sulfur or NR<1><0>; Y is oxygen or NR<1><0>; Z is hydrogen, hydroxy, C1-4 alkyl, C1-4alkoxy, -NR<7>R<8>, amino(C1-4)alkyl, azido(C1-4)alkyl or hydroxy (C1-4)alkyl; R<7> and R<8> each are independently hydrogen, C1-4 alkyl or alkanoyl; and R<1><0> is hydrogen, C1-4 alkyl, C1-4 alkylamino or di(C1-4)alkylamino; or a non-toxic pharmaceutically acceptable salt thereof, are novel antimicrobial agents which are useful in the treatment of infectious disease in humans and other animals. Novel intermediates and processes for their preparation are also disclosed.