Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti- Wolbachia Drug Candidate for a Short-Course Treatment of Filariasis
Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti- Wolbachia Drug Candidate for a Short-Course Treatment of Filariasis
复制标题
AWZ1066S 的制造工艺从发现到公斤级的转变：用于短期治疗丝虫病的高度特异性抗沃尔巴克氏体候选药物
DOI：
10.1021/acs.oprd.2c00167
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
Hong W
中科院分区：
文献类型：
--
作者：
Hong W
抗沃尔巴克氏体疗法已被临床证明是治疗盘尾丝虫病和淋巴丝虫病的安全方法。 AWZ1066S 是一种一流的高度特异性抗 Wolbachadrug 候选药物，专为人类丝虫病的短期治疗而开发，现已进入临床开发阶段。描述了一种改进的、具有成本效益的、可扩展的生产该临床候选药物的工艺。本文介绍的是活性药物成分（API）及其两种关键起始原料[2-（三氟甲基）-3-吡啶基]甲胺和（S）-3-甲基吗啉的工艺开发工作，从2,4-二氯吡啶并[2,3-d]嘧啶开始，能够一致地提供高纯度（>99%）的API。优化的生产路线用于公斤级临床候选药物的生产，以支持正在进行的临床开发。
Anti-Wolbachiatherapy has been clinically proven to be a safe approach for the treatment of onchocerciasis and lymphatic filariasis. AWZ1066S, a first-in-class highly specific anti-Wolbachiadrug candidate developed for a short-course treatment of human filariasis, has advanced into clinical development. An improved, cost-efficient, and scalable process for the manufacture of this clinical candidate is described. Presented herein is the process development work for the active pharmaceutical ingredient (API) and its two key starting materials [2-(trifluoromethyl)-3-pyridyl]methanamine and (S)-3-methylmorpholine, starting from 2,4-dichloropyrido[2,3-d]pyrimidine, which is capable of delivering high-purity (>99%) API consistently. The optimized production route was used in the manufacture of the clinical candidate at the kilogram scale to support the ongoing clinical development.