Reaction Kinetics for the Synthesis of an Anti-Cancer Drug (Adavosertib) Precursor

Abstract

The development of kinetic models which can accurately describe drug synthesis is an essential part of process design in the pharmaceutical industry. Correctly identifying these models can be difficult, however, since the reaction pathways required to manufacture new pharmaceutical compounds are often extremely complex. Consequently, kinetic modelling and parameter estimation tools have become a key part of the design process for drug manufacturers looking to bring new molecular entities (NMEs) to market; since they provide a convenient way of testing a variety of candidate reaction models before selecting the one which provides the best predictions. In light of this, in this work, an in-house parameter estimation code written in MATLAB R2018a using multiple start-point search methodologies has been used to parameterise a range of kinetic models thought to be capable of describing the synthesis of a key intermediate required for the manufacture a new anti-cancer drug, Adavosertib (AZD1775). Meanwhile, Akaike and Bayesian information criteria have been used to identify which of these models provide the best fit whilst also maintaining model simplicity.

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