Abstract
A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated.
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Alihodzic, S., Fajdetic, A., Kobrehel, G. et al. Synthesis and Antibacterial Activity of Isomeric 15-Membered Azalides. J Antibiot 59, 753–769 (2006). https://doi.org/10.1038/ja.2006.100
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DOI: https://doi.org/10.1038/ja.2006.100
Keywords
- azalide
- ketolide
- acylide
- antibacterial activity
- structure-activity relationship
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