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Discovery of triazole aminopyrazines as a highly potent and selective series of PI3Kdelta inhibitors
A novel class of potent PI3Kdelta inhibitors with >1000-fold selectivity against other class I PI3K isoforms is described. Optimization of the substituents on a triazole aminopyrazine scaffold, emerging from an in-house PI3Kalpha program, turned moderately selective PI3Kdelta compounds into highly potent and selective PI3Kdelta inhibitors. These efforts resulted in a series of aminopyrazines with PI3Kdelta IC50???1?nM in the enzyme assay, some of the most selective PI3Kdelta inhibitors published to date, with a cell potency in a JeKo-cell assay of 20?120?nM.
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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics