Patent Evaluation: Benzenesulphonamide derivatives as 5-lipoxygenase inhibitors

Abstract

Novelty: Novel benzenesulfonamide derivatives are claimed for the treatment of leukotriene mediated disorders with a process for their preparation. They are potentially useful for the treatment of allergic conditions such as psoriasis, asthma, cardiovascular and cerebrovascular disorders and inflammatory and arthritic conditions.

Biology: 5LPO inhibition was measured by the method of Carey et ul. (Prosruglandins, Leukotriene Med. (1986) 2257) and the specified compound gave an IC₅₀ value of 1 pM against LTB₄. An ex vivo variation of this test using rats is described but no specific results are presented. In vivo the effect of the compound on LTB₄ liberation induced in rats by zymosan was measured. The specified compound gave an oral ED₅₀ of 1.5 mgkg against LTB₄.

Chemistry: Preparation is described in three schemes, exemplified in fifteen cases and forms subsidiary part of the claim. Six compounds are specifically claimed including 4-[3-(4-methoxytetrahydropyran-4-yl)phenylthio]-N-(%-thiazolyl)benzene sulphonamide.