Toward the Development of a Commercial Process to Produce Muvalaplin. Part II: Preparation of the Drug Substance

IF 3.3 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2026-10-16 Epub Date: 2026-09-22 DOI:10.1021/acs.oprd.6c00323

Daniel P. Walker, John R. Rizzo, Mai Khanh Hawk, Matthew J. Genzink, Antonio Navarro, Dajiang Jing, Srinivas Gangula, Silong Zhang, Jianfei Dai, Panpan Sun

引用次数: 0

Abstract

Herein, we describe the development of steps 5–7 for a large-scale process to synthesize muvalaplin, a small-molecule lipoprotein(a) inhibitor for the potential reduction of major adverse cardiovascular events in participants with established cardiovascular disease or at risk for a first cardiovascular event. Each step was optimized, leading to improvements in safety, robustness, and cost of goods that ultimately resulted in a 41% yield increase over three steps and a 60% reduction in PMI compared to the original discovery synthesis. The process was safely scaled to >100 kg, thus ensuring clinical supply and laying the foundation for a commercial route.

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Muvalaplin商业化生产工艺的探讨。第二部分：原料药的制备

本文中，我们描述了大规模合成muvalaplin的步骤5-7的发展，muvalaplin是一种小分子脂蛋白(a)抑制剂，用于潜在地减少已确定心血管疾病或有首次心血管事件风险的参与者的主要不良心血管事件。每个步骤都经过优化，从而提高了安全性、稳健性和产品成本，与最初的发现合成相比，三步合成的收率提高了41%，PMI降低了60%。该过程被安全地扩展到&；gt；100公斤，从而保证临床供应，为商业路线奠定基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.