Potent and highly selective benzimidazole inhibitors of PI3-kinase delta

…, D Chantry, M Flagella, DM Goldstein…

Index: Murray, Jeremy M.; Sweeney, Zachary K.; Chan, Bryan K.; Balazs, Mercedesz; Bradley, Erin; Castanedo, Georgette; Chabot, Christine; Chantry, David; Flagella, Michael; Goldstein, David M.; Kondru, Rama; Lesnick, John; Li, Jun; Lucas, Matthew C.; Nonomiya, Jim; Pang, Jodie; Price, Stephen; Salphati, Laurent; Safina, Brian; Savy, Pascal P. A.; Seward, Eileen M.; Ultsch, Mark; Sutherlin, Daniel P. Journal of Medicinal Chemistry, 2012 , vol. 55, # 17 p. 7686 - 7695

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Citation Number: 31

Abstract

Inhibition of PI3Kδ is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3Kδ. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3Kδ inhibitors. Instead, the selectivity of ...