George Karageorgis*, James J. Douglas and Gareth P. Howell,
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引用次数: 0
Abstract
The assessment of molecular complexity of active pharmaceutical ingredients (APIs) can help guide decisions within drug development, for example, by correlation to sustainability targets, project resource requirements, and predicted development and manufacturing timelines. However, such quantifications are limited by the challenge of defining complexity itself as well as the small sample size of API molecules making longer term comparisons challenging. We have used four complementary approaches to calculate the complexity of reaction products of more than 165,000 reaction entries across our process development electronic laboratory notebooks. Importantly, this dataset covers both intermediates, APIs, and other molecules requiring synthesis, thus, attempts to provide an analysis of reaction products from all our synthetic chemistry activities. This information facilitated the investigation of changes in the mean values of different measures of molecular complexity per year between 2007 and 2020. We discuss the insights these quantifications reveal and how this analysis may be of more general use in understanding the diversity of the molecules in our process development portfolio.
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.