1,5-Disubstituted indazol-3-ols with anti-inflammatory activity

A series of new indazol-3-ol derivatives was synthesized. Some of these compounds exhibit interesting anti-inflammatory activities in various models of inflammation. 5-Methoxy-1-(quinoline-2-yl-methoxy)-benzyl]-1H-indazol-3-ol (27) strongly inhibits the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid catalyzed by 5-lipoxygenase (IC 50 =44 nM). 27 also inhibits the contraction of sensitized guinea pig tracheal segments (IC 50 = 2.9 μM). In guinea pigs treated with 27 (1 mg/kg i.p.) 2 h before antigen provocations there was a marked inhibition (47%) of the antigen-induced airway eosinophilia. After topical application of 1 μg/ear 27 inhibits the arachidonic acid induced mouse ear edema (41%).