TY - JOUR
T1 - 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
AU - Hong, W. David
AU - O’Neill, Paul M.
AU - Taylor, Mark
AU - Turner, Joseph
AU - Ward, Steve
AU - Gusovsky, Fabian
AU - Benayoud, Farid
AU - Shibuguchi, Nao
AU - Girish, Dixit
AU - Fang, Francis Gerard
AU - Talabhakthla, Ravi Kumar
AU - Vaddi, Anand
AU - Challa, Chiranjeevi
AU - Reddy, Karri Satya Ammi
AU - Kalla, Vijay
AU - Srinivasa Rao, Sugandham
AU - Nagireddi, Durga Mahesh Kumar
AU - Patel, Jayesh
AU - Khile, Anil Shahaji
PY - 2024/1/10
Y1 - 2024/1/10
N2 - 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.
AB - 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.
KW - anti-Wolbachia
KW - AWZ1066S
KW - chiral morpholine analogue
KW - filariasis
KW - trifluoromethyl pyridine derivative
U2 - 10.1021/acs.oprd.2c00167
DO - 10.1021/acs.oprd.2c00167
M3 - Review article
SN - 1083-6160
VL - 27
SP - 42
EP - 53
JO - Organic Process Research and Development
JF - Organic Process Research and Development
IS - 1
ER -