Patent Evaluation: Novel Sulphonamide 5-Lipoxygenase Inhibitors

Summary

Novelty: Novel sulphonamide derivatives which are inhibitors of the enzyme 5-lipoxygenase (5-LPO) are disclosed. Processes for their manufacture and pharmaceutical compositions containing them are given. The compounds are potentially useful in the treatment of inflammatory and allergic diseases.

Biology: The effect of 5-LPO inhibition was evaluated using three procedures. Test (a) was an in vitro assay which involved incubating the compound with heparinized human blood. Test (b) was an ex vivo assay, and test (c) an in vivo system involving the measurement of the effects of a test compound administered orally against the liberation of LTB₄. The exemplified compound has an IC₅₀ of 0.09 μM against LTB₄ in test (a) and an oral ED₅₀ of 1 mg/kg versus LTB₄ in test (c).

Chemistry: Eight compounds are exemplified including N-(3-chloro-4-[3-(4-methoxytetrahydropyran-4-yl)phenylthio]phenyl)-N-methylmethanesulphonamide.

Structure: