Patent Evaluation: Vitamin E Analogues as Anti-Oxidants for the Treatment of Atherosclerosis

Summary

Novelty: Anti-oxidant 1-benzopyran-4-one derivatives are disclosed. Such agents have free-radical scavenging activity similar to that of vitamin E and are potentially useful for ameliorating ischaemic, autoimmune and cirrhotic damage. The principle claim, however, is the use of these compounds to inhibit oxidation of low-density lipoprotein (LDL) which underlies the pathogenesis of atherosclerosis.

Biology: Inhibition of Cu²⁺-catalysed LDL oxidation in plasma samples is demonstrated with IC₅₀ values 10^–5 -10^–7 M, comparable to vitamin E (IC₅₀= 4.8 μM). Inhibition of MEP-G2 cell culture synthesis of cholesterol with IC₅₀ values 10^–8 -10^–9 M is also demonstrated.

Chemistry: Ten preparative schemes are presented, forming a subsidiary claim 2-(4-Fluorophenyl)-3-(2-thiaoctadecyl)-5, 7-dihydroxy-4A-1-benzopyran-4-one is a preferred example.

Structure: