Central Process Development Department (EL-OTS) Merck KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.
R&D Department, Valiant Pharmaceutical Co. Ltd., Taiyuan Road No. 60, YEDA, Yantai, Shandong, 264006, China.
ChemMedChem. 2023 Jun 15;18(12):e202300154. doi: 10.1002/cmdc.202300154. Epub 2023 Apr 18.
Investigations on praziquantel (PZQ) started fifty years ago by a cooperation between Bayer AG and Merck KGaA. Until today PZQ is the drug of choice for schistosomiasis in human medicine and used in many combinations with antinematode drugs in veterinary medicine. The Sm.TRPM , a Ca -permeable transient receptor potential (TRP) channel, has been discovered as primary target of PZQ during the last decade. Furthermore, there is a short overview of routes of large-scale synthesis of racemic and pure (R)-PZQ. Until now racemic PZQ is used in veterinary and human medicine. In 2012 the Pediatric Praziquantel Consortium started PZQ chemistry and process development of pure (R)-PZQ for human application. It is hoped that (R)-PZQ will become available for pediatric use soon. The knowledge of the binding pocket of PZQ in Sm.TRPM allows to design synthesis of PZQ-derivatives of the next generation for a target-site directed screening. A similar screening should also be started for Fasciola hepatica TRPM .
吡喹酮（PZQ）的研究始于五十年前，由拜耳公司（Bayer AG）和默克公司（Merck KGaA）合作开展。直到今天，PZQ 仍然是人类医学中治疗血吸虫病的首选药物，并在兽医医学中与许多抗线虫药物联合使用。Sm.TRPM 是一种钙通透性瞬时受体电位（TRP）通道，在过去十年中被发现是 PZQ 的主要靶标。此外，本文还简要概述了大规模合成外消旋和纯（R）-PZQ 的路线。到目前为止，外消旋 PZQ 仍在兽医和人类医学中使用。2012 年，儿科吡喹酮联盟开始了纯（R）-PZQ 的化学和工艺开发，以用于人类应用。人们希望（R）-PZQ 很快就能用于儿科。对 Sm.TRPM 中 PZQ 结合口袋的了解，使得能够针对靶标定向筛选来设计合成下一代 PZQ 衍生物。也应该针对肝片形吸虫 TRPM 开始类似的筛选。
