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DOI: 10.1055/s-0042-1751502
Development of a Practical Synthetic Method for Clinical Candidate 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy} phenyl)propanoic acid (P218) and Its Hydroxylated Metabolites
This research was supported by the Program Management Unit for Human Resources & Institutional Development, Thailand Science Research and Innovation, NXPO (grant number B47Q660105), National Science and Technology Development Agency (NSTDA, National Center for Genetic Engineering and Biotechnology; grant number P1850116), and the Global Health Innovative Technology Fund (GHIT; grant number T2021-152).
Abstract
3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751502.
- Supporting Information
Publikationsverlauf
Eingereicht: 05. Juli 2023
Angenommen nach Revision: 23. August 2023
Artikel online veröffentlicht:
30. Oktober 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)
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