Design,synthesis and structure-activity relationship of imidazo[1,2-a]pyrimidine-based human urate transporter inhibitors
LOU Jin-fang
LI Da-wei
XU Si-cong
CHEN Qiang
ZHANG Jin-zhu
ZHANG Jian
LI Yuan-yuan
TAN Shi-jie
GUO Jun-kai
SHAO Qian
LIU Xue-song
MIAO Lei
Abstract：The aim of this study is to design and synthesize benzbromarone(BBR)derivatives targeting human urate anion transporter 1(hURAT1)inhibition and to investigate their structure-activity relationship(SAR).Based on BBR's SAR and hepatotoxicity mechanisms,structural optimization was performed using computer-aided drug design(CADD).The synthesized compounds were structurally characterized by 1 H-NMR and LC-MS/MS.hURAT1 inhibitory activities were evaluated by stable hURAT1 cell models.A series of compounds featuring imidazo[1,2-a]pyrimidine core structures were obtained,with compound 1 and 10 demonstrating potent hURAT1 inhibitory activity.The rational design strategy employed in this study demonstrates scientific validity,provides deeper insights into the SAR of hURAT1 inhibitors,validates the complex relationship between chemical structure and inhibitory activity,and offers crucial references for developing next-generation antihyperuricemic agents.
Keywords：human urate anion transporter 1molecular designbiological activitycomputer-aided drug designstructure-activity relationship
Publication Date：2025-10-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 2217-2223 )