Synthesis of some 5-phenylisoxazole-3-carboxylic acid derivatives as potent xanthine oxidase inhibitors.
A number of 5-phenylisoxazole-3-carboxylic acid derivatives (5a-e, 11a-e) were synthesized and analyzed for their ability to inhibit xanthine oxidase. Most of the compounds exhibited potency levels in the micromolar/submicromolar range. The presence of a cyano group at the 3-position of phenyl moiety turned out to be the preferred substitution pattern, as its transformation into the nitro group determined a general reduction of the inhibitory potency. A molecular modeling study on compound 11a was performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non-purine xanthine oxidase inhibitors related with 5-phenylisoxazole-3-carboxylic acid scaffold.
Wang
Shaojie
S
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China. sjwang_99@yahoo.com.cn
Yan
Jufang
J
Wang
Jian
J
Chen
Jiarun
J
Zhang
Tingjian
T
Zhao
Yong
Y
Xue
Mingxing
M
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
C550869:5-phenylisoxazole-3-carboxylic acid; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D014969:Xanthine Oxidase