Thermal Stability Assessment of Peptide Coupling Reagents Commonly Used in Pharmaceutical Manufacturing

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2018-07-30 DOI:10.1021/acs.oprd.8b00193

Jeffrey B. Sperry*, Christopher J. Minteer, JingYa Tao, Rebecca Johnson, Remzi Duzguner, Michael Hawksworth, Samantha Oke, Paul F. Richardson, Richard Barnhart, David R. Bill, Robert A. Giusto, John D. Weaver III

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引用次数: 61

Abstract

Amide couplings are one of, if not the most common chemical reactions performed in the pharmaceutical industry. Many amide bonds are generated with the help of highly active peptide coupling reagents. These reagents have garnered wide use in the pharmaceutical industry, but many contain high-energy functional groups. As a result, significant time is spent assessing the thermal stability of these reagents before scale-up commences. This paper assesses the thermal stability of 45 common peptide coupling reagents by differential scanning calorimetry and accelerating rate calorimetry. Those compounds which flagged as potentially impact-sensitive or potentially explosive were tested by drop hammer and explosivity screening techniques. The data are presented in an effort to drive the development of these reactions toward the use of one of the more thermally stable reagents.

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医药生产常用肽偶联试剂的热稳定性评价

酰胺偶联是制药工业中最常见的化学反应之一。许多酰胺键是在高活性肽偶联试剂的帮助下产生的。这些试剂在制药工业中得到了广泛的应用，但许多含有高能官能团。因此，在开始按比例放大之前，需要花费大量时间来评估这些试剂的热稳定性。采用差示扫描量热法和加速量热法对45种常用肽偶联试剂的热稳定性进行了评价。那些被标记为潜在冲击敏感或潜在爆炸性的化合物通过落锤和爆炸性筛选技术进行了测试。这些数据的提出是为了推动这些反应朝着使用一种更热稳定的试剂的方向发展。

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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.