Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors.
A series of 1-phenylpyrazoles was evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme inhibition and displayed longer-lasting hypouricemic action than did allopurinol in a rat model of hyperuricemia induced by the uricase inhibitor potassium oxonate.
Ishibuchi
S
S
Drug Discovery Research Laboratories, Welfide Corporation, Osaka, Japan. ishibuchi@welfide.co.jp
Morimoto
H
H
Oe
T
T
Ikebe
T
T
Inoue
H
H
Fukunari
A
A
Kamezawa
M
M
Yamada
I
I
Naka
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D006073:Gout / Q000188:drug therapy; D006074:Gout Suppressants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000188:drug therapy; D023421:Models, Animal; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014503:Urate Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014527:Uric Acid / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
C433950:1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid; D006074:Gout Suppressants; D011720:Pyrazoles; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase; D014503:Urate Oxidase