Design, synthesis and biological evaluation of inhibitors of urate transporter 1 (URAT1)
10.16438/j.0513-4870.2019-0208
- VernacularTitle:尿酸盐转运体1抑制剂的设计、合成及活性研究
- Author:
Yong-cheng WANG
1
;
Ya-jun YANG
1
;
Xian-xin HOU
1
;
Ying YANG
1
;
Zhi-yan XIAO
1
Author Information
1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
URAT1 inhibitors;
hyperuricemia;
gout;
URC-102 analogs
- From:
Acta Pharmaceutica Sinica
2019;54(6):1069-1074
- CountryChina
- Language:Chinese
-
Abstract:
Urate transporter 1 (URAT1) is a validated target for the treatment of hyperuricemia. Based on the structure of URC-102, which is currently under a phase Ⅱ clinical trial, fourteen novel analogs were designed and synthesized. Among them, four compounds (9b, 9c, 10e and 10g) exhibited substantial inhibitory effect against URAT1. The most active compound 9b showed an IC50 value of 0.061 μmol·L-1, which is significantly more potent than Lesinurad and Benzbromarone. Preliminary SAR was drawn, providing clues for further structural optimization.
