engleski

Novel Ureas and Thioureas of 15-membered Azalides with antibacterial activity against key respiratory pathogens

The new ureas and thioureas of 15-membered azalides, N’ ’ substituted 9a-(N’ -carbamoyl-γ - aminopropyl) (4), 9a-(N’ -thiocarbamoyl-γ - aminopropyl) (6), 9a-[N’ -(β -cyanoethyl)-N’ - (carbamoyl-γ -aminopropyl)] (8) and 9a-[N’ -(β - cyanoethyl)-N’ -(thiocarbamoyl-γ -aminopropyl)] (10) of 9-deoxo-9-dihydro-9a-aza-9a- homoerythromycin A (2), were synthesized and structurally characterized by NMR and IR spectroscopic methods and mass spectrometry. The new compounds were evaluated in vitro against a panel of erythromycin-susceptible and erythromycin-resistant Gram-positive and Gram- negative bacterial strains. These compounds 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. In addition, several ureas with naphtyl substituents (4f, 4g, 4h) showed better activity in comparison to azithromycin against inducible resistant S. pyogenes. Ureas with naphtyl substituents 4g, 4h and thiourea 8h displayed moderate activity against constitutively resistant S. pneumoniae.

Azalides; ureas; thioureas; structure elucidation; antibacterial activity

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