Chemical Biology and Drug Design
Chemical Biology and Drug Design
5 years ago

Design, synthesis and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as xanthine oxidase inhibitors

Design, synthesis and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as xanthine oxidase inhibitors
Fan-hao Meng, Qing-xia Wu, Yi Zhang, Song-ye Li, Ting-jian Zhang
A series of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives (1a-p) was designed, synthesized and identified as xanthine oxidase inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC50 values of 8.1 μM and 6.7 μM, respectively. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type xanthine oxidase inhibitor. SARs analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom; and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The basis of xanthine oxidase inhibition by 1k was rationalized by molecular modeling studies. This article is protected by copyright. All rights reserved. The little compounds were designed, synthesized and identified as XO inhibitors. SARs analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom, and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type xanthine oxidase inhibitor and the molecular modeling studies rationalized the basis of XO inhibition by 1k.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13114

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