STUDIES ON CEPHALOSPORIN ANTIBIOTICS III. SYNTHESIS, ANTIBACTERIAL ACTIVITY AND ORAL ABSORPTION OF NEW 3-(SUBSTITUTED-ALKYLTHIO)-7j8-[(Z)-2-(2-AMINOTHIAZOL-4-YL)- 2-(CARBOXYMETHOXYIMINO)ACETAMIDO] CEPHALOSPORINS
نویسندگان
چکیده
The synthesis, antibacterial activity and oral absorption in rats of new 7/?-[(Z)-2-(2-aminothiazol4-yl)-2-(carboxymethoxyimino)acetamido]cephalosporins (1) having various substituted-alkylthio groups at the C-3 position of the cephemnucleus are described. Of these, the cephalosporins with a cyanomethylthio group (Id) and fluoroethylthio group (lp) at the C-3 position showed a potent in vitro antibacterial activity against Gram-positive and Gram-negative bacteria as well as good oral absorption in rats. Whenadministered orally to mice infected with Klebsiella pneumoniae, Id had stronger protective effect than lp. The structure-activity relationships of 1 are also presented.
منابع مشابه
STUDIES ON CEPHALOSPORIN ANTIBIOTICS IV. SYNTHESIS, ANTIBACTERIAL ACTIVITY AND ORAL ABSORPTION OF NEW 3-(2-SUBSTITUTED-VINYLTHIO)-7j5- [(Z)-2-(2-AMINOTHIAZOL-4-YL)-2-
A series of new 7j5-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido]cephalosporins (1) having various substituted-vinylthio groups at the C-3 position of the cephem nucleus was synthesized and evaluated for antibacterial activity and oral absorption in rats in comparison with cefixime. Of these, the cephalosporins (la and lc) with a lower alkoxycarbonylvinylthio group (Z-form) at ...
متن کاملSynthesis and antibacterial activity of 7-[2-(2-aminooxazol-4-yl)-(Z)-2-alkoxyiminoacetamido]-cephalosporin antibiotics.
In a previous paper3), we reported on the synthesis and the biological activity of 3-methoxymethyl cephalosporin derivatives, one of which, cefpodoxime proxetil (Fig. 1), has been successfully developed as a prodrug for oral use. Our further elaboration for developing orally active cephalosporins has been made in the direction of chemical modification of the C-7 acyl substituent of the 3-methox...
متن کاملStudies on orally active cephalosporins. II. Synthesis and structure-activity relations of new [(E) or (Z) 3-substituted carbamoyloxy]-1-propenyl cephalosporins.
In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and b...
متن کاملSTUDIES UN UKALLYACTIVE UliFMAJLUSrUKirM liS l liKS VIf. SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF 3-( 3-ISOXAZOLYL)OXYMETHYLCEPHALOSPORIN DERIVATIVES
The synthesis and biological activities of a series of 3-(isoxazol-3-yl)oxymethyl cephalosporins are described. 7[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido] -3[ (isoxazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid (7a) showedpotent activity against both Gram-positive and Gram-negative bacteria including some /3-lactamase producing species. Its pivaloyloxymethyl ester provided a good u...
متن کاملCGP 9000: a new orally active, broad-spectrum cephalosporin.
CGP 9000, (7-[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-3-cephem-4-carboxylic acid), is a new broad-spectrum cephalosporin antibiotic. Its antibacterial activity in vitro (MIC) is similar, but its bactericidal efficacy superior to that of cephalexin and cephradine. Upon oral administration to mice infected with various bacteria, CGP 9000 is, in general, 2 to 7 times more effective ...
متن کامل