Improved synthesis of the thiophenol precursor N-(4-chloro-3-mercaptophenyl)picolinamide for making the mGluR4 PET ligands

Autor:	Junfeng Wang, Timothy M. Shoup, Zhaoda Zhang, Anna-Liisa Brownell
Rok vydání:	2019
Předmět:	Reaction conditions 010405 organic chemistry Chemistry Thiophenol Organic Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry 0104 chemical sciences chemistry.chemical_compound Yield (chemistry) Drug Discovery Radioligand
Zdroj:	Tetrahedron. 75:3917-3922
ISSN:	0040-4020
DOI:	10.1016/j.tet.2019.06.010
Popis:	Recently [11C]mG4P012 (previously [11C]KALB012 and presently named as [11C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and l -dopa-induced dyskinesia. [11C]mG4P012 was shown to be a promising PET radioligand for mGluR4 in the monkey brain and for further development in human subjects. However, the previously reported multi-step synthesis of the thiophenol precursor suffered from low yields and difficult workup procedures. To support the translational research of [11C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::2453f849ab87761acf6db0c5064d5138 https://doi.org/10.1016/j.tet.2019.06.010 Zobrazit plný text záznamu Full Text from ScienceDirect