（±）-雷西纳德的阻转异构体的发现与评估
Discovery and Assessment of Atropisomers of (±)-Lesinurad.
作者信息
Wang Jianfei, Zeng Wenqin, Li Shaohua, Shen Liang, Gu Zhengxian, Zhang Yang, Li Jian, Chen Shuhui, Jia Xiangbo
机构信息
WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, P. R. China.
Sagacity New Drug R&D Co., Ltd. , 18 Zhenze Road, Xinwu District, Wuxi, Jiangsu 214135, P. R. China.
出版信息
ACS Med Chem Lett. 2017 Feb 14;8(3):299-303. doi: 10.1021/acsmedchemlett.6b00465. eCollection 2017 Mar 9.
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 human recombinant CYP2C9 stability studies. It was speculated that (+)-lesinurad might offer a better hyperuricemia/gout therapy than (-)-lesinurad or the racemate.
摘要
首次从外消旋雷西纳德中分离出（+）-和（-）-雷西纳德作为阻转异构体。在各种测试条件下，未观察到两种阻转异构体之间的相互转化。在基于高表达hURAT1的HEK293细胞的抑制试验、猴子药代动力学研究和人重组CYP2C9稳定性研究中，这两种阻转异构体表现出显著差异。据推测，（+）-雷西纳德可能比（-）-雷西纳德或外消旋体提供更好的高尿酸血症/痛风治疗效果。
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