ANHYDROLIDE MACROLIDES - 2 - SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 2,3-ANHYDRO-6-O-METHYL 11,12-CARBAZATE ERYTHROMYCIN-A ANALOGS

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11,12 -cyclic carbazate analogues was prepared and evaluated for antibacteri al activity. These 2,3-anhydro macrolides were found to be potent anti bacterial agents in vitro against macrolide-susceptible organisms incl uding Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and S treptococcus pneumoniae ATCC6303. These compounds were also very activ e against some organisms that show macrolide resistance (S. aureus A51 77, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds genera lly showed poor activity against organisms with constitutive MLS resis tance. Selected compounds were evaluated in vivo in mouse protection s tudies. Although most of the compounds tested in vivo showed poor effi cacy, two compounds, 38 and 57, were more active than clarithromycin a gainst S. pneumoniae ATCC6303.