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

Autor:	Lin H; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Schulz MJ; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Xie R; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Zeng J; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Luengo JI; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Squire MD; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Tedesco R; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Qu J; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Erhard K; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Mack JF; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Raha K; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Plant R; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Rominger CM; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Ariazi JL; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Sherk CS; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Schaber MD; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., McSurdy-Freed J; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Spengler MD; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Davis CB; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Hardwicke MA; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States., Rivero RA; Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2012 May 29; Vol. 3 (7), pp. 524-9. Date of Electronic Publication: 2012 May 29 (Print Publication: 2012).
DOI:	10.1021/ml300045b
Abstrakt:	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.
Databáze:	MEDLINE
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