Patent Evaluation: Dual acting TxA Synthase Inhibitors/TxA Antagonists

Summary

Novelty: Novel pyridyl derivatives are disclosed and are claimed to be useful for the treatment and the prophylaxis of thromboembolic diseases, arteriosclerosis, ischaemia and asthma.

Biology: The antithrombotic and thromboxane antagonism effects of the compounds were assayed. The acute toxicity and the ability of the compounds to inhibit thromboxane synthetase (IC₅₀ = 4 nM) were also determined. In an assay of the inhibition of collagen-induced platelet aggregation, a specified compound exhibited an EC₅₀ = 0.5 μM.

Chemistry: Syntheses of the compounds are described in twelve examples using conventional methods. (-)-5E-6[4-(Z-2-(4-chlorophenyl)-cyclopropyl-l-carboxamido)-phenyl]-6-(3-pyridyl)-hex-5-enoic acid is one of four specifically claimed examples.

Structure: