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

ABSTRACT: 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.

SUBMITTER: Lin H

PROVIDER: S-EPMC4025772 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other

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

Lin Hong H Schulz Mark J MJ Xie Ren R Zeng Jin J Luengo Juan I JI Squire Michael D MD Tedesco Rosanna R Qu Junya J Erhard Karl K Mack James F JF Raha Kaushik K Plant Ramona R Rominger Cynthia M CM Ariazi Jennifer L JL Sherk Christian S CS Schaber Michael D MD McSurdy-Freed Jeanelle J Spengler Michael D MD Davis Charles B CB Hardwicke Mary Ann MA Rivero Ralph A RA

ACS medicinal chemistry letters 20120529 7

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. ...[more]

PMID: 24900504

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