Synthesis and biological properties of 3-[()-2-(1,2,3-Thiadiazolyl)ethenyl]-substituted cephalosporins and related compounds: new oral cephalosporins

Bioorganic & Medicinal Chemistry Letters
1993.0

Abstract

A series of cephalosporins possessing a [(a-2-(1,2,3-thiadiazolyl)ethenyl] moiety at C-3 were synthesized and their biological propem'es were examined. SC-002 (la) exhibited excellent activity against both Gram-positive and Gram-negative bacteria. The ester SC-004 (lb) showed good bioavailability after oral administration in mice and rats. Although many orally active cephalosporins are used in clinical practice, the number of cephalosporins possessing broad spectrum antibiotic activity is limited. Therefore compounds having a well balanced antibacterial spectrum as well as high potency are still needed. Recently, orally active cephalosporins have been reported, which have at C-3 a vinyll, (Z)-2-propenyl*, or (Z)-2-(4-methylthiazol-5-yl)ethenylJ moiety and exhibit strong antibiotic activities. We became interested in the 123-thiadiazole group at C-3' of cefuzonam, an injectable cephalosporin extremely active against Gram-positive bacteriaP and found that introduction of the 1,2,3_thiadiazolylethenyl moiety at C-3 led to compounds showing remarkably potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Herein, we report the synthesis and the biological properties of a series of cephalosporins of this type.

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