AB-343原料药可扩展制造工艺的开发：治疗冠状病毒感染的潜在候选药物

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-02-25 DOI:10.1021/acs.oprd.4c00528

Jeremy D. Mason, Jan M. Spink, Mahesh Pallerla, Zhenhua Wu, Rajeev K. Singh, Aravind B. Pulipaka, Jia Liu, Marvin Marcus Vega, Xu Wang, Michael J. Sofia, Ganapati Reddy Pamulapati

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引用次数: 0

摘要

已开发出抗冠状病毒临床候选药物AB-343的可扩展生产工艺。采用一种新的合成路线，包括硝基-迈克尔反应和铑催化的硝基加氢，然后进行原位翻译酰胺化序列作为关键转化，制备了该分子的含内酰胺亚基。该原料药通过连续的酰胺偶联和脱保护反应组装，然后使用T3P将伯胺脱水成相应的腈。AB-343原料药已成功地以多公斤规模生产，适用于支持ind研究和I期临床开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections

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Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections

A scalable process for manufacturing of the anticoronavirus clinical candidate AB-343 has been developed. The lactam-containing subunit of the molecule was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation. The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P. AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clinical development.

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.