Kilogram-Scale Synthesis and Impurity Profiling of a COPD Candidate LY104: Optimization of Salt Forms for Enhanced Purity and Pharmaceutical Potential

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-06-16 DOI:10.1021/acs.oprd.5c00123

Jilong Zhang, Kaile Li, Xiaokun Liu, Ping Zhang, Wanli Meng, Shengbiao Wan, Guanhua Du, Jiejie Hao, De Wang

引用次数: 0

Abstract

This study describes a synthetic route to access LY104, a structurally novel compound investigated for the treatment of chronic obstructive pulmonary disease (COPD). Our approach to LY104 encompasses (i) a concise and efficient synthetic strategy for this COPD candidate and (ii) a scalable process with structural characterization of related impurities. The synthesis of LY104 was accomplished in four steps, during which three key impurity structures were identified. Through careful optimization of the chemical process, LY104 acetate salt was consistently obtained in a high purity (>99.85%) for pharmacological studies.

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慢性阻塞性肺病候选药物LY104的公斤级合成和杂质分析：优化盐形式以提高纯度和药物潜力

本研究描述了一种获得LY104的合成途径，LY104是一种结构新颖的化合物，用于治疗慢性阻塞性肺疾病（COPD）。我们对LY104的研究方法包括(i)对这种COPD候选药物的简洁有效的合成策略和（ii）对相关杂质进行结构表征的可扩展过程。LY104的合成分四个步骤完成，其中鉴定了三个关键杂质结构。通过精心优化化学工艺，连续获得高纯度（99.85%）的LY104醋酸盐，用于药理研究。

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.