Synthesis of some 5-phenylisoxazole-3-carboxylic acid derivatives as potent xanthine oxidase inhibitors. 2010

Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
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

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.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D002264 Carboxylic Acids Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. Carboxylic Acid,Acid, Carboxylic,Acids, Carboxylic
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014969 Xanthine Oxidase An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase

Related Publications

Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
July 2018, European journal of medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
April 2008, European journal of medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
November 2017, European journal of medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
December 2004, Acta poloniae pharmaceutica,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
July 2017, Bioorganic & medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
October 2014, European journal of medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
August 2017, Bioorganic & medicinal chemistry letters,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
February 2017, Archiv der Pharmazie,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
November 2019, European journal of medicinal chemistry,
Shaojie Wang, and Jufang Yan, and Jian Wang, and Jiarun Chen, and Tingjian Zhang, and Yong Zhao, and Mingxing Xue
April 2016, Chemical biology & drug design,
Copied contents to your clipboard!