Patent Evaluation: Novel Piperidines as PAF Antagonists

Summary

Novelty: Imidazobenzazepines or imidazopyridoazepines, which bear an optionally N-substituted piperidine moiety, are disclosed. The compounds are claimed to be potent antagonists of platelet aggregating factor (PAF) and are potentially useful for the treatment of asthma, bronchitis and other chronic obstructive airways disease. The compounds may also have more general potential use as anti-allergic and anti-inflammatory agents.

Biology: The PAF antagonism of the compounds was demonstrated by inhibition of PAF-induced platelet aggregation in human platelet-rich plasma; IC₅₀ values for selected compounds were in the range 5-35 μM. In vivo utility of the compounds was assayed by the suppression of PAF-induced bronchospasm in guinea pigs. However, no specific data are provided.

Chemistry: Synthesis of the compounds was by conventional ring-closure and derivatization methods, which are exemplified in four cases, and form a subsidiary part of the claim. Four compounds are specifically claimed, including the preferred compound 4-(5,6-dihydro-¹11H-imidazo[2,1-b] [3]benzazepin-11-ylidene)-1-(4-pyridinylcarbonyl)piperidine-N′-oxide.

Structure: