Inhibitors of alpha-chymotrypsin derived from cephalosporins: structure-activity relationships

Cephalothin and certain other cephalosporins are irreversible inhibitors of alpha-chymotrypsin in near neutral media. The active inhibiting species is slowly generated in small yield from cephalothin in aqueous solution. Structure-activity studies for 37 other cephalosporins and related compounds establish that inhibitors of the enzyme require in the parent cephalosporin molecule a 7-acyl substituent containing a flat area in the form of an aromatic or heterocyclic ring together with a 3-acetoxymethyl or other substituent which is labile to water. The inhibitory species is considered to be the oxazolinone derived from the corresponding cephalosporoic acid.