Balancing Yield, Purity, and Form: Finding the Sweet Spot for the Rework of the First Clinical Batch of Giredestrant (GDC-9545)

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2023-11-15 DOI:10.1021/acs.oprd.3c00256

Paroma Chakravarty*, Jie Xu, Brandon Scott, Sarah J. Robinson and Karthik Nagapudi,

引用次数: 0

Abstract

Giredestrant (GDC-9545) is a selective estrogen receptor degrader that was developed as a tartrate salt. The first GMP batch was manufactured via a crystallization-driven diastereoselective Pictet–Spengler condensation. This batch underwent an additional rework step due to inherent challenges involving purity, yield, and preservation of the desired polymorphic form. This study outlines the solid-state characterization experiments conducted to identify the appropriate route and solvent composition for the required rework to deliver a drug substance clinical batch with the desired polymorphic form, yield, and purity.

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平衡产量、纯度和形式：为第一临床批次吉瑞司群 (GDC-9545) 的返工找到最佳点

Giredestrant (GDC-9545) 是一种选择性雌激素受体降解剂，以酒石酸盐的形式开发。第一个 GMP 批次是通过结晶驱动的非对映选择性 Pictet-Spengler 缩合反应生产的。由于在纯度、产量和所需多晶型的保存方面存在固有挑战，该批次产品又经历了一个返工步骤。本研究概述了所进行的固态表征实验，这些实验的目的是为所需的返工确定合适的路线和溶剂成分，以提供具有所需多晶型、产率和纯度的药物临床批次。

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.