Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371259 | Bioorganic & Medicinal Chemistry Letters | 2012 | 7 Pages |
Abstract
Herein we describe the SAR of a novel series of 6-aryl-2-amino-triazolopyridines as potent and selective PI3Kγ inhibitors. The 6-aryl-triazolopyridine core was identified by chemoproteomic screening of a kinase focused library. Rapid chemical expansion around a bi-functional core identified the key features required for PI3Kγ activity and selectivity. The series was optimized to afford 43 (CZC19945), a potent PI3Kγ inhibitor with high oral bioavailability and selectivity over PI3Kα and PI3Kδ. Modification to the core afforded 53 (CZC24832) which showed increased selectivity over the entire kinome in particular over PI3Kβ.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Kathryn Bell, Mihiro Sunose, Katie Ellard, Andrew Cansfield, Jess Taylor, Warren Miller, Nigel Ramsden, Giovanna Bergamini, Gitte Neubauer,