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[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase ? Inhibitors.

ABSTRACT: A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3K?. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey.

SUBMITTER: Yu H

PROVIDER: S-EPMC4027147 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors.

Yu Hongyi H Moore Michael L ML Erhard Karl K Hardwicke Mary Ann MA Lin Hong H Luengo Juan I JI McSurdy-Freed Jeanelle J Plant Ramona R Qu Junya J Raha Kaushik K Rominger Cynthia M CM Schaber Michael D MD Spengler Michael D MD Rivero Ralph A RA

ACS medicinal chemistry letters 20130110 2

A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3Kβ. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey. ...[more]

PMID: 24900655

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