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Synthesis and Evaluation of Imidazo[1,2‐ a ]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3‐Kinase Inhibitors
Author(s) -
Gamage Swarna A.,
Spicer Julie A.,
Tsang Kit Y.,
O'Connor Patrick D.,
Flanagan Jack U.,
Lee WooJeong,
Dickson James M. J.,
Shepherd Peter R.,
Denny William A.,
Rewcastle Gordon W.
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201801762
Subject(s) - benzimidazole , chemistry , pyridine , selectivity , phosphatidylinositol , kinase , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry
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.