2. Academic Validation
  3. Discovery and Assessment of Atropisomers of (±)-Lesinurad

Discovery and Assessment of Atropisomers of (±)-Lesinurad

  • ACS Med Chem Lett. 2017 Feb 14;8(3):299-303. doi: 10.1021/acsmedchemlett.6b00465.
Jianfei Wang 1,  Wenqin Zeng 1,  Shaohua Li 1,  Liang Shen 1,  Zhengxian Gu 1,  Yang Zhang 1,  Jian Li 1,  Shuhui Chen 1,  Xiangbo Jia 2
Affiliations

Affiliations

  • 1 WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
  • 2 Sagacity New Drug R&D Co., Ltd. , 18 Zhenze Road, Xinwu District, Wuxi, Jiangsu 214135, P. R. China.
PMID: 28337320 DOI: 10.1021/acsmedchemlett.6b00465
Abstract

(+)- and (-)-Lesinurad were isolated as atropisomers from racemic lesinurad for the first time. No interconversion was observed between the two atropisomers under various conditions tested. The two atropisomers showed significant differences in hURAT1 highly expressed HEK293 cell-based inhibition assays, monkey pharmacokinetic studies, and in vitro human recombinant CYP2C9 stability studies. It was speculated that (+)-lesinurad might offer a better hyperuricemia/gout therapy than (-)-lesinurad or the racemate.

Keywords

Atropisomer; gout; hyperuricemia; lesinurad.

Figures