engleski

Synthesis and biological activity of novel sulfonylureas, ureas and thioureas of 15-membered azalides

In spite of a numerous existing macrolide antibiotics, such as azithromycin (1), the emerging multidrug resistant microbial pathogens present serious and challenging problems in medical treatment which demand novel and more effective antimicrobial agents to be discovered. A series of novel sulfonylureas, ureas and thioureas of 15-membered azalides, were discovered, structurally characterized and biologically evaluated[1]. These include 9a-N-[N’-(aryl)sulfonylcarbamoyl]- (2), 9a-N-{;N’-[(aryl)- sulfonylcarbamoyl-γ-aminopropyl]};- (3), and 9a-N-{;N’-(β-cyanoethyl)-N’-[(aryl)sulfonyl- carabamoyl-γ-aminopropyl]};- (4), N’’ substituted 9a-(N’-carbamoyl-γ-aminopropyl)- (5, 7), 9a-(N’-thiocarbamoyl-γ-aminopropyl)- (6, 8), 9a-[N’-(β-cyanoethyl)-N’-(carbamoyl-γ-aminopropyl)]- (9, 11), 9a-[N’-(β-cyanoethyl) -N’-(thiocarbamoyl-γ-aminopropyl)]-(10, 12) derivatives. Ureas 5, 7 and thioureas 6, 8 displayed an excellent overall antibacterial in vitro activity against erythromycin sensitive Gram-positive strains, S. pneumoniae, S. pyogenes, S. aureus, and good against negative strains, M. catarrhalis and H. influenzae. Several sulfonylureas 2 and ureas 5 showed significant improvements in antibacterial activity against inducible resistant Streptococcus pyogenes strain. Among the synthesized compounds some thioureas 8 and urea 11 have shown substantially improved activity comparable to 1 against efflux-mediated resistant S. pneumoniae.

macrolide antibiotics; sulfonylurea; urea; thiourea

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