Design, synthesis and biological activity of tetrazole-bearing uric acid transporter 1 inhibitors

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).

Keywords

URAT1 inhibitor / Structure-activity relationship / Drug discovery / Lesinurad / Tetrazole / Bioisostere

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