[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase 尾 Inhibitors
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- 作者：Hongyi Yu ; Michael L. Moore ; Karl Erhard ; Mary Ann Hardwicke ; Hong Lin ; Juan I. Luengo ; Jeanelle McSurdy-Freed ; Ramona Plant ; Junya Qu ; Kaushik Raha ; Cynthia M. Rominger ; Michael D. Schaber ; Michael D. Spengler ; Ralph A. Rivero
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：February 14, 2013
- 年：2013
- 卷：4
- 期：2
- 页码：230-234
- 全文大小：293K
- 年卷期：v.4,no.2(February 14, 2013)
- ISSN：1948-5875
文摘
A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3K尾. 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.