engleski

Synthesis and Antibacterial Activity of Isomeric 15- Membered Azalides

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.

azalide; ketolide; acylide; antibacterial activity; structure-activity relationship

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