SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF NOVEL 3-[(AMINOPYRIMIDINIUMYL)THIO]METHYL CEPHALOSPORINS

A series of novel cephalosporin compounds which have 3-[(aminopyrimidi niumyl)thio]methyl substituents was synthesized. They show high antimi crobial activity against various bacterial species including Pseudomon as aeruginosa. Structure-activity relationships with various thiopyrim idines, thiopyrimidiniums, bicyclic thiotriazolopyrimidiniums, and bic yclic thioimidazolopyrimidiniums as 3'-substituents were also studied; cephalosporins with quarternized pyrimidinium moieties have better an timicrobial activities than neuteral pyrimidine cephalosporins, and st abilization of the positive charge on the pyrimidinium moieties is ess ential for better activity. According to semiempirical PM3 calculation s, amino and alkylthio substituents on the pyrimidinium rings play a m ajor role in charge stabilization and delocalization.