Synthesis and Evaluation of Imidazo[1,2‐a]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3‐Kinase Inhibitors

Autor:	James M. J. Dickson, Swarna A. Gamage, Julie Ann Spicer, Kit Yee Tsang, Woo-Jeong Lee, Gordon W. Rewcastle, William A. Denny, Patrick D. O'Connor, Peter R. Shepherd, Jack U. Flanagan
Rok vydání:	2019
Předmět:	Benzimidazole Pyridines Stereochemistry 010402 general chemistry 01 natural sciences Biochemistry Phosphatidylinositol 3-Kinases Structure-Activity Relationship chemistry.chemical_compound Heck reaction Pyridine Humans Phosphatidylinositol Enzyme Inhibitors Phosphoinositide-3 Kinase Inhibitors Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Kinase Hydrogen bond Organic Chemistry Biological activity General Chemistry 0104 chemical sciences chemistry Selectivity
Zdroj:	Chemistry – An Asian Journal. 14:1249-1261
ISSN:	1861-471X 1861-4728
DOI:	10.1002/asia.201801762
Popis:	Using a scaffold-hopping approach, imidazo[1,2-a]pyridine analogues of the ZSTK474 (benzimidazole) class of phosphatidylinositol 3-kinase (PI3K) inhibitors have been synthesized for biological evaluation. Compounds were prepared using a heteroaryl Heck reaction procedure, involving the palladium-catalysed coupling of 2-(difluoromethyl)imidazo[1,2-a]pyridines with chloro, iodo or trifluoromethanesulfonyloxy (trifloxy) substituted 1,3,5-triazines or pyrimidines, with the iodo intermediates being preferred in terms of higher yields and milder reaction conditions. The new compounds maintain the PI3K isoform selectivity of their benzimidazole analogues, but in general show less potency.
Databáze:	OpenAIRE
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