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
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
Author
Vorasin O. Phumjan T. Saepua S. Iwaniuk D. Kamchonwongpaisan S. Yuthavong Y. Thongpanchang C. Srimongkolpithak N.
Affiliations
National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency 111 Thailand Science Park (TSP) Phahonyothin Road Khlong Nueng Khlong Luang Pathum Thani 12120 Thailand
Type
Article
Source Title
Synthesis (Germany)
ISSN
397881
Year
2023
Volume
55
Issue
23
Page
3947-3953
Open Access
All Open Access Hybrid Gold
Publisher
Georg Thieme Verlag
DOI
10.1055/s-0042-1751502
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. ? 2023. The Author(s).
