Practical application of 3-substituted-2, 6-difluoropyridines in drug discovery: Facile synthesis of novel protein kinase C theta inhibitors. Issue 11 (1st June 2017)

• Record Type: Journal Article
• Authors: Katoh, Taisuke; Tomata, Yoshihide; Setoh, Masaki; Sasaki, Satoshi; Takai, Takafumi; Yoshitomi, Yayoi; Yukawa, Tomoya; Nakagawa, Hideyuki; Fukumoto, Shoji; Tsukamoto, Tetsuya; Nakada, Yoshihisa
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 11(2017)
• Page Start: 2497
• Page End: 2501
• Publication Date: 2017-06-01
• Subjects: 3-Substituted-2, 6-difluoropyridine -- 2, 3, 6-Trisubstituted pyridine -- PKCθ inhibitor -- Macrocyclic derivatives -- Drug design; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.099
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We previously reported a facile preparation method of 3-substituted-2, 6-difluoropyridines, which were easily converted to 2, 3, 6-trisubstituted pyridines by nucleophilic aromatic substitution with good regioselectivity and yield. In this study, we demonstrate the synthetic utility of 3-substituted-2, 6-difluoropyridines in drug discovery via their application in the synthesis of various 2, 3, 6-trisubstituted pyridines, including macrocyclic derivatives, as novel protein kinase C theta inhibitors in a moderate to good yield. This synthetic approach is useful for the preparation of 2, 3, 6-trisubstituted pyridines, which are a popular scaffold for drug candidates and biologically attractive compounds.