Design, Synthesis and Biological Activity of Tetrazole-bearing Uric Acid Transporter 1 Inhibitors

doi:10.1007/s40242-017-6351-3

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (1): 49-60.doi: 10.1007/s40242-017-6351-3

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Design, Synthesis and Biological Activity of Tetrazole-bearing Uric Acid Transporter 1 Inhibitors

CAI Wenqing^1,2, LIU Wei², XIE Yafei², WU Jingwei², LIU Yuqiang², LIU Changying², XU Weiren², TANG Lida², WANG Jianwu¹, ZHAO Guilong²

1. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China;
2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P. R. China

Received:2016-08-23 Revised:2016-09-28 Online:2017-02-01 Published:2017-01-19
Contact: WANG Jianwu,E-mail:jwwang@sdu.edu.cn;ZHAO Guilong,E-mail:zhao_guilong@126.com E-mail:jwwang@sdu.edu.cn;zhao_guilong@126.com
Supported by:
Supported by the Key Projects of Tianjin Science and Technology Support Plan, China(No.16YFZCSY00910) and the Natural Science Foundation of Shandong Province, China(No.ZR2015BM028).

Abstract

Abstract:

Systematic structure-activity relationship(SAR) exploration of a moderately active tetrazole-bearing lesinurad-based hit 1f led to the discovery of a potent uric acid transporter 1(URAT1) inhibitor 1i, which possessed a novel molecular skeleton and was 11-fold more potent than the parent lesinurad against human URAT1 in-vitro (IC₅₀=0.66 μmol/L for 1i vs. 7.18 μmol/L for lesinurad).

Key words: URAT1 inhibitor, Structure-activity relationship, Drug discovery, Lesinurad, Tetrazole, Bioisostere

CAI Wenqing, LIU Wei, XIE Yafei, WU Jingwei, LIU Yuqiang, LIU Changying, XU Weiren, TANG Lida, WANG Jianwu, ZHAO Guilong. Design, Synthesis and Biological Activity of Tetrazole-bearing Uric Acid Transporter 1 Inhibitors[J]. Chemical Research in Chinese Universities, 2017, 33(1): 49-60.

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Design, Synthesis and Biological Activity of Tetrazole-bearing Uric Acid Transporter 1 Inhibitors

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