SYNTHESIS AND IN-VITRO EVALUATION OF NEW CEPHALOSPORINS EXHIBITING ANTIMICROBIAL ACTIVITY AGAINST GRAM-POSITIVE BACTERIA, IN PARTICULAR METHICILLIN-RESISTANT STAPHYLOCOCCI

The preparation and biological evaluation of 7 -[[2-(phenyl)thiazol-4- yl]acetamido]cephalosporins and 7 beta-[[2-(pyridin-2-yl)thiazol-4-yl] acetamido] cephalosporins, 9a-o, substituted at the c-position with a cetyloxymethyl, chlorine, hydrogen, and methyl are described. Hantzsch 's thiazole synthesis is employed to provide thiazoleacetic acids 5a-e , subsequently followed by Morpho CDI-assisted amidation to complete t he synthesis of target cephalosporins 9a-o. These compounds display ac tivity selectively against Grampositive bacteria, but are inactive aga inst most Gram-negative bacteria tested. Those with acetyloxymethyl at the 3-position, i.e., 9a, 9e, 9i, 9m, and 9o, exhibit activity with m inimal inhibitory concentrations of 16 mu g/mL or lower against four s trains of methicillin-resistant staphylococci, namely Staphylococcus a ureus X400 and S13E and Staphylococcus epidermidis 270 and 222. Notabl y, 9a displays an activity profile similar to that of vancomycin regar ding its spectrum and potency.