Patent Evaluation: Erythromycin Antibacterial Agents

Summary

Novelty: A novel method of preparing novel 9-deoxo-8a-aza-8a-homoerythromycin A and its 8a-alkyl derivatives, and 8a-aza-8a-homoerthythromycin cylic iminoethers is claimed. The compounds are antibiotics and may be used to treat bacterial infections; they may also be used as intermediates for the synthesis of other compounds.

Biology: Antibacterial activity of two compounds was assayed against fifteen bacterial strains in vitro. MIC values were determined turbidimetrically in brain heart infusion broth and are 0.06 to 128 μg/ml for the preferred compound. The spectrum of activity of the compounds is said to be similar to erythromycin A. Their in vivo activity is more limited, although they are active against Gram-positive and certain Gram-negative bacteria.

Chemistry: Synthesis is by multistep reactions by standard techniques, starting from 8a-aza-8a-homoerythromycin cyclic iminoethers (in EP-508726-A) and 9-deoxy-9(Z)-hydroxyiminoerythromycin A (in EP-508725-A). Eleven examples are given in each application. Characterization is by mp, IR, NMR, MS and elemental analysis. The preferred compound is 9-deoxo-8a-methyl-8a-aza-8a-homoerythromycin A (in EP-508726-A) and 9-deoxy-6,9-epoxy-8a,9-didehydro-8a-aza-8a-homoerthromycin A (in EP-508725-A).