Patent Evaluation: Quinoline 5-Lipoxygenase Inhibitors

Summary

Novelty: 2-Substituted quinolines are disclosed which are active as inhibitors of 5-lipoxygenase (5-LPO). These compounds are potentially useful as inhibitors of inflammation, allergic responses and airways hyper-reactivity, as well having potential use for the prevention of thromboembolism and ischaemic damage.

Biology: Inhibition of 5-LPO was demonstrated by suppression of leukotriene LTB₄ production by Ca²⁺-ionophore-stimulated polymorphonuclear lymphocytes; IC₅₀ values for selected compounds were between 0.56-2.50 μM.

Chemistry: Synthesis of the compounds comprises reaction of a 2-halogenomethylquinoline with an appropriately substituted phenol derivative. Forty-three preparative examples are given, together with seventy-nine final compounds. Synthesis of the compounds forms a subsidiary part of the claim. No compounds are specifically claimed. 2-[3-Fluoro-4-(quinolin-2-methoxy)phenyl]-2-cyclopentylacetic acid methyl ester is an active and exemplified compound.

Structure: