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Novel azalides derived from 16-membered macrolides. III. Azalides modified at the C-15 and 4'' positions: Improved
Tomoaki Miura1, Satomi Natsume, Kenichi Kanemoto
1Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. tomoaki_miura@meiji.co.jp
Abstract:
The design and synthesis of 16-membered azalides modified at the C-15 and 4'' positions are described. The compounds we report here are characterized by an arylpropenyl group attached to the C-15 position of macrolactone and a carbamoyl group at the C-4'' position in a neutral sugar. Introduction of alkylcarbamoyl groups to the C-4'' position was regioselectively achieved by unique and convenient methods via acyl migration. As a result of optimization at the C-3 and 15 positions, several compounds were found to have potent activity against mef- and erm-resistant bacterial strains. These results suggest that 16-membered azalides could be promising compounds as clinical candidates.
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