Document Detail


Synthesis of some 5-phenylisoxazole-3-carboxylic acid derivatives as potent xanthine oxidase inhibitors.
MedLine Citation:
PMID:  20189693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shaojie Wang; Jufang Yan; Jian Wang; Jiarun Chen; Tingjian Zhang; Yong Zhao; Mingxing Xue
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Publication Detail:
Type:  Journal Article     Date:  2010-02-10
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  45     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-20     Completed Date:  2010-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  France    
Other Details:
Languages:  eng     Pagination:  2663-70     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.
Affiliation:
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
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MeSH Terms
Descriptor/Qualifier:
Animals
Carboxylic Acids / chemical synthesis*,  chemistry,  pharmacology*
Cattle
Enzyme Inhibitors / chemical synthesis*,  chemistry,  pharmacology*
Humans
Isoxazoles / chemical synthesis*,  chemistry,  pharmacology*
Models, Molecular
Molecular Conformation
Structure-Activity Relationship
Xanthine Oxidase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/5-phenylisoxazole-3-carboxylic acid; 0/Carboxylic Acids; 0/Enzyme Inhibitors; 0/Isoxazoles; EC 1.17.3.2/Xanthine Oxidase

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