AZALIDES - SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NOVEL 9A-N-(N'-SUBSTITUTED CARBAMOYL AND THIOCARBAMOYL) DERIVATIVES OF 9-DEOXO-9-A-AZA-9A-HOMOERYTHROMYCIN-A

A series of 9a-N-(N'-substituted carbamoyl and thiocarbamoyl) derivati ves of 9-deoxo-9a-aza-9a-homoerythromycin A was synthesized and struct urally characterized by spectroscopic methods and X-ray crystallograph ic analysis. The new compounds were evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria and their antibacterial a ctivities compared with those of the parent 9a-amine 2 and azithromyci n 3. The results indicate that this type of structural modification of fers no benefit over 2 and that the potency of the majority of these c ompounds in vitro decreased in comparison with 3. Among the tested aza lides, the N'-isopropylcarbamoyl derivative 4 and the N'-benzylthiocar bamoyl derivative 12 showed the most potent antibacterial in vitro act ivity.