Synthesis and antibacterial activity of novel lincomycin derivatives. III. Optimization of a phenyl thiadiazole moiety

Lincomycin derivatives that have a 5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl thio moiety at the 7-position were synthesized. 5-Substituted 2-nitrophenyl derivatives showed potent antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene. Antibacterial activities of the 4,5-di-substituted 2-nitrophenyl derivatives were generally comparable to those of telithromycin (TEL) against S . pneumoniae with erm gene and clearly superior to those of TEL against S . pyogenes with erm gene. Compounds 6 and 10c that have a methoxy group at the 5-position of the benzene ring exhibited activities comparable to TEL against Haemophilus influenzae . These results suggest that lincomycin derivatives modified at the 7-position would be promising compounds as a clinical candidate. We would like to dedicate this article to the special issue for late Professor Dr. Hamao Umezawa in The Journal of Antibiotics .