ABSTRACT
Some (alpha-hydrazinobenzyl)cephalosporins, I (R = Me, CH2OAc, Cl) and II (R = Me, CH2OAc), structurally related (formula; see text) to cephalexin, cephaloglycin, and cefaclor have been prepared and evaluated in vitro for their antimicrobial activity. The synthesis involves the condensation of the chloride hydrochloride III (R = H or Me) with the 7-aminocephem derivatives IV. The hydrazino compound I (R = Cl), an analogue of cefaclor, resulted in being the most active compound of the series.
Subject(s)
Cephalosporins/chemical synthesis , Bacteria/drug effects , Cefaclor/analogs & derivatives , Cefaclor/chemical synthesis , Cefaclor/toxicity , Cephalexin/analogs & derivatives , Cephalexin/chemical synthesis , Cephalexin/toxicity , Cephaloglycin/analogs & derivatives , Cephaloglycin/chemical synthesis , Cephaloglycin/toxicity , Cephalosporins/toxicity , Hydrazines/chemical synthesis , Hydrazines/toxicity , Indicators and Reagents , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrophotometry, Infrared , Structure-Activity RelationshipABSTRACT
Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain have been prepared by nucleophilic substitution of 7-aminocephalosporanic acid with appropriate azine thiols followed by 7-N-acylation with phenylglycine by the mixed anhydride method. Seventeen thiols of non-substituted or substituted pyridines, pyridazines, pyrimidines, pyrazines and triazines were used as the S-nucleophiles. In general, pyridazine thiols gave cephalosporins processing good antimicrobial activity against both gram-positive and gram-negative bacteria. Among them 6-hydroxypyridazine-3-thiol gave the most active compound of this series, BB-S 118 (1f), which was significantly more active than cephalexin and cephaloglycin in vitro against gram-positive and gram negative bacteria.
