Discovery and Assessment of Atropisomers of (±)-Lesinurad.
(+)- 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, andin vitrohuman recombinant CYP2C9 stability studies. It was speculated that (+)-lesinurad might offer a better hyperuricemia/gout therapy than (-)-lesinurad or the racemate.
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Jianfei
J
Wang
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Wenqin
W
Zeng
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Shaohua
S
Li
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Liang
L
Shen
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Zhengxian
Z
Gu
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Yang
Y
Zhang
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Jian
J
Li
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Shuhui
S
Chen
Sagacity New Drug R&D Co., Ltd. , 18 Zhenze Road, Xinwu District, Wuxi, Jiangsu 214135, P. R. China.
Xiangbo
X
Jia
Atropisomer; gout; hyperuricemia; lesinurad