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 (IC50 = 44 nM). 27 also inhibits the contraction of sensitized guinea pig tracheal segments (IC50 = 2.9 microM). In guinea pigs treated with 27 (1 mg/kg i.p.) 2 h before antigen provocation, there was a marked inhibition (47%) of the antigen-induced airway eosinophilia. After topical application of 1 microgram/ear 27 inhibits the arachidonic acid induced mouse ear edema (41%).
Schindler
R
R
Department of Chemical Research, Corporate R&D, ASTA Medica Group, Arzneimittelwerk Dresden GmbH, Radebeul, Germany.
Fleischhauer
I
I
Höfgen
N
N
Sauer
W
W
Egerland
U
U
Poppe
H
H
Heer
S
S
Szelenyi
I
I
Kutscher
B
B
Engel
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D004802:Eosinophilia / Q000188:drug therapy; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007191:Indazoles