氘代沃拉帕沙的设计与合成

Design and synthesis of deuterium-labeled vorapaxar

摘要: 沃拉帕沙(vorapaxar)是一种新型蛋白酶激活受体1(PAR-1)拮抗剂，可抑制凝血过程。氘代沃拉帕沙作为内标可满足临床样品分析检测的需要。本文以未标记的沃拉帕沙为起始原料，经过水解、缩合、酯交换和氢氘交换4步反应首次高效地合成以D₈为主的氘代沃拉帕沙。所有中间体和终产物均经过核磁和高分辨质谱确证，所制备氘代化合物［D₈］沃拉帕沙满足内标化合物的使用要求。
- 沃拉帕沙 /
- 稳定同位素标记 /
- 氢-氘交换 /
- 内标 /
- PAR-1拮抗剂 /
- 抗血小板药物
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 standard. 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). Importantly, the prepared ［D₈］ vorapaxar could meet the requirements of sample analysis as the internal standard.
- vorapaxar /
- stable isotope labeling /
- hydrogen-deuterium exchange /
- internal standard /
- PAR-1 antagonist /
- antiplatelet agents

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