Patent Evaluation: Novel N-hydroxyureas as 5-lipoxygenase Inhibitors

Summary

Novelty: A novel series of aromatic hydroxyureas and methods of preparation are disclosed. These compounds are claimed for use in lipoxygenase-mediated disease (e.g. arthritis, rheumatoid arthritis, osteoarthritis, allergic rhinitis etc.).

Biology: Human monocytes are used to generate IC₅₀ data for 5-LPO, LTB₄ and PGE7 (5-LPO, IC₅₀=0.5–48 μM). Results are also given for ex vivo percent inhibition of PGQ writhing (ED₅₀=7.7 to greater than 20 mg/kg).

Chemistry: Extensive synthetic details are given for the preparation of this class of compound with forty-four examples. Forty-three derivatives are named within the claims and these include N-1-(6-benzyloxy-1,2,3,4-tetrahydronaphthyl)-N-hydroxyamine and N-1-(5-benzyloxyindanyl)-N-hydroxyamine.

Structure: