Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti-Wolbachia Drug Candidate for a Short-Course Treatment of Filariasis



Hong, W David, O'Neill, Paul M ORCID: 0000-0003-4338-0317, Taylor, Mark J, Turner, Joseph D, Ward, Stephen A, Gusovsky, Fabian, Benayoud, Farid, Shibuguchi, Nao, Girish, Dixit, Fang, Francis Gerard
et al (show 9 more authors) (2023) Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti-Wolbachia Drug Candidate for a Short-Course Treatment of Filariasis. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 27 (1). pp. 42-53.

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Abstract

Anti-Wolbachia therapy has been clinically proven to be a safe approach for the treatment of onchocerciasis and lymphatic filariasis. AWZ1066S, a first-in-class highly specific anti-Wolbachia drug candidate developed for a short-course treatment of human filariasis, has advanced into clinical development. An improved, cost-efficient, and scalable process for the manufacture of this clinical candidate is described. Presented herein is the process development work for the active pharmaceutical ingredient (API) and its two key starting materials [2-(trifluoromethyl)-3-pyridyl]methanamine and (S)-3-methylmorpholine, starting from 2,4-dichloropyrido[2,3-d]pyrimidine, which is capable of delivering high-purity (>99%) API consistently. The optimized production route was used in the manufacture of the clinical candidate at the kilogram scale to support the ongoing clinical development.

Item Type: Article
Uncontrolled Keywords: anti-Wolbachia, AWZ1066S, chiral morpholine analogue, filariasis, trifluoromethyl pyridine derivative
Divisions: Faculty of Science and Engineering > School of Physical Sciences
Depositing User: Symplectic Admin
Date Deposited: 15 May 2023 07:32
Last Modified: 10 Jan 2024 02:30
DOI: 10.1021/acs.oprd.2c00167
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3170326