Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors

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• 作者：Hong Lin ; Mark J. Schulz ; Ren Xie ; Jin Zeng ; Juan I. Luengo ; Michael D. Squire ; Rosanna Tedesco ; Junya Qu ; Karl Erhard ; James F. Mack ; Kaushik Raha ; Ramona Plant ; Cynthia M. Rominger ; Jennifer L. Ariazi ; Christian S. Sherk ; Michael D. Schaber ; Jeanelle McSurdy-Freed ; Michael D. Spengler ; Charles B. Davis ; Mary Ann Hardwicke ; Ralph A. Rivero
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：July 12, 2012
• 年：2012
• 卷：3
• 期：7
• 页码：524-529
• 全文大小：354K
• 年卷期：v.3,no.7(July 12, 2012)
• ISSN：1948-5875

文摘

A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been identified. This chemotype has provided an excellent tool compound, 18, that showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage-independent conditions, and it also demonstrated pharmacodynamic effects and efficacy in a PTEN-deficient prostate cancer PC-3 xenograft mouse model.

Keywords:

d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=PI3K%5C-beta+inhibitor&qsSearchArea=searchText">PI3K-beta inhibitor; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=PTEN%5C-deficient&qsSearchArea=searchText">PTEN-deficient; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=phosphatidylinositol+3%5C-kinase&qsSearchArea=searchText">phosphatidylinositol 3-kinase; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=homology+model&qsSearchArea=searchText">homology model; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=structure%E2%80%93activity+relationship&qsSearchArea=searchText">structure鈥揳ctivity relationship