Synthesis and antibacterial activity of novel lincomycin derivatives. IV. Optimization of an N-6 substituent

The design and synthesis of lincomycin derivatives modified at the C-6 and C-7 positions are described. A substituent at the C-7 position is a 5-aryl-1,3,4-thiadiazol-2-yl-thio group that generates antibacterial activities against macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes carrying an erm gene. An additional modification at the C-6 position was explored in application of information regarding pirlimycin and other related compounds. These dual modifications were accomplished by using methyl α-thiolincosaminide as a starting material. As a result of these dual modifications, the antibacterial activities were improved compared with those of compounds with a single modification at the C-7 position. The antibacterial activities of selected compounds in this report against macrolide-resistant S. pneumoniae and S. pyogenes with an erm gene were superior to those of telithromycin.