Development of a Scalable Synthesis of a Drug-Linker for ABBV-3373

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-03-05 DOI:10.1021/acs.oprd.3c00447

Nathan B. Bennett*, Bradley D. Gates, Justin A. Simanis, James W. Treadway, Steven M. Richter and Dennie S. Welch,

引用次数: 0

Abstract

A scalable process to produce glucocorticoid-bearing drug-linker 1, utilized in the conjugation with the monoclonal antibody (mAb) adalimumab, has been developed. The route improves upon the first-generation approach through a more convergent assembly of the linker and warhead. Optimization and insights into the key transformations are discussed, including a challenging acetonide deprotection, acetal formation under strongly acidic conditions, and amide coupling and purification.

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开发 ABBV-3373 药物连接剂的可扩展合成方法

我们开发出了一种可扩展的工艺，用于生产与单克隆抗体（mAb）阿达木单抗共轭的含糖皮质激素药物连接体1。这条路线通过连接体和弹头更趋同的组装，改进了第一代方法。本文讨论了关键转化过程的优化和见解，包括具有挑战性的丙酮脱保护、强酸性条件下的缩醛形成以及酰胺偶联和纯化。

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.