Patent Evaluation: Hydroxylamine derivatives as lipoxygenase inhibitors

Summary

Novelty: Novel substituted heteroaryl hydroxylamine derivatives are claimed to be lipoxygenase (LPO) inhibitors. They are said to be particularly effective against 5-LPO. They are potentially useful for the treatment of inflammatory and allergic disorders, asthma, dermatitis, ischaemia and endotoxin shock.

Biology: 5-LPO inhibition was determined by measuring the inhibition of the synthesis of 5-HETE and LTB₄ in guinea-pig polymorphonuclear leukocytes. Methods to measure antiinflammatory and anti-asthmatic activity are also described. However, no specific biological data are presented.

Chemistry: A total of eighty-six compounds are disclosed. Syntheses are given in thirteen examples. Nine compounds are specifically claimed including 2-[3-(4-fluorophenyl)propyl]-6-[2-(N-aminocarbonyl-N-hydroxyamino)ethoxy]-1-oxo-1,2,3,4-tetrahydroisoquinoline.