Orally active cephalosporins. Part 3: Synthesis, structure-activity relationships and oral absorption of novel C-3 heteroarylmethylthio cephalosporins

A series of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3- (heteroarylmethylthio)cephalosporins was designed, synthesized and evaluate d for antibacterial activity and oral absorption in rats. Antibacterial act ivity was markedly influenced by the structure of the heteroaromatic ring m oiety. Oral absorption was influenced by the heteroaromatic ring moiety as well as by the arrangement of heteroatoms. Among these compounds, FK041 (2o ). having a 4-pyrazolylmethylthio moiety, showed potent antibacterial activ ity against both Gram-positive and Gram-negative bacteria including Haemoph ilus influenzae. Further, it showed higher oral absorption than CFDN. (C) 2 001 Elsevier Science Ltd. All rights reserved.