Design and synthesis of deuterium-labeled vorapaxar
10.11665/j.issn.1000-5048.20180307
- VernacularTitle:氘代沃拉帕沙的设计与合成
- Author:
Yu HUANG
1
;
Baomin LIU
;
Xushi LIU
;
Yinsheng ZHANG
Author Information
1. 正大天晴药业集团股份有限公司
- Keywords:
vorapaxar;
stable isotope labeling;
hydrogen-deuterium exchange;
internal standard;
PAR-1 antago-nist;
antiplatelet agents
- From:
Journal of China Pharmaceutical University
2018;49(3):295-300
- CountryChina
- Language:Chinese
-
Abstract:
Vorapaxar,a novel antagonist of the protease-activated receptor 1 (PAR-1 ),can inhibit the clotting process. Deuterium-labeled vorapaxar was required for the analysis of clinical sample as an internal stand-ard. Starting for unlabeled vorapaxar,four-step reactions including hydrolysis,condensation,transesterification and hydrogen-deuterium exchange were carried out to synthesize [D8]vorapaxar effectively for the first time. All intermediates and final products were confirmed by NMR and high resolution mass spectrometry (HRMS).Impor-tantly,the prepared [D8]vorapaxar could meet the requirements of sample analysis as the internal standard.
