Patent Evaluation: Antibacterial Condensed Carbapenems

Summary

Novelty: Novel condensed carbapenems are described. These compounds, containing an amidine group, are claimed to have antibacterial activity and are potentially useful in the treatment or prophylaxis of systemic or topical infections. A process for the synthesis of these tricyclic carbapenems is also claimed.

Biology: The specific compound is shown to have antibacterial activity against Gram-positive bacteria (MIC 0.1-1 μg/ml), Gram-negative bacteria (E. coli 1852E 0.5 μg/ml, Ps. aeruginosa 1911E 8 μg/ml) and also anaerobes (B. fragilis 2017E 0.2 μg/ml). No adverse effects were observed in toxicological studies in mouse and rat at 500 mg/kg iv.

Chemistry: The syntheses of seven intermediates and two examples by modification of known methods are fully detailed. Only one compound is specifically claimed, (4S,8S,9R,10S,12R)-4-(N-methylformamidino)-10-(1-hydroxyethyl)-11-oxo-1-azatricyclo[7.2.0.0³⁸]undec-2-ene-2-carboxylic acid.