Orally active cephalosporins. part 2: Synthesis, structure-activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain

A series of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]cep halosporins having a pyridine ring connected through various spacer moietie s at the C-3 position was designed and synthesized and evaluated for antiba cterial activity and oral absorption in rats. All compounds showed potent a ntibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spac er moiety between the pyridine and cephem nucleus. Oral absorption was infl uenced by the position of the pyridine nitrogen as well as by the spacer mo iety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moi ety at the C-3 position, showed the most well balanced activity and moderat e oral absorption. (C) 2000 Elsevier Science Ltd. All rights reserved.