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

Summary

Novelty: Acetylenic N-hydroxyureas are disclosed and are stated to be 5-lipoxygenase inhibitors, which are potentially suitable for treating diseases such as asthma, rhinitis, rheumatoid arthritis, psoriasis, ARCs and inflammatory bowel disease.

Biology: In vitro 5-LPO inhibition was determined using an RBL supernatant assay; IC₅₀ values are given for fifty-five compounds. In vivo activity was determined in a rat peritoneal anaphylaxis model with results given for thirty-seven compounds. N-hydroxy-N-[4-[5-(4-fluorophenyl)-2-furyl]-3-butyn-2-yl]urea has an IC₅₀ of 0.2 μM and showed 83% inhibition at 30 μmol/kg po

Chemistry: The syntheses of 157 examples and eighteen intermediates are described in full. One hundred and forty-six compounds are explicitly claimed with N-hydroxy-N-[4-[5-(4-fluorophenoxy)-2-furyl-3-butyn-2-yl]urea and its enantiomers.

Structure: