Discovery of Potent, Efficient, and Selective Inhibitors of Phosphoinositide 3-Kinase δ through a Deconstruction and Regrowth Approach.

Autor:	Barton N; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Convery M; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Cooper AWJ; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Down K; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Hamblin JN; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Inglis G; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Peace S; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Rowedder J; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Rowland P; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Taylor JA; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K., Wellaway N; GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2018 Dec 27; Vol. 61 (24), pp. 11061-11073. Date of Electronic Publication: 2018 Dec 21.
DOI:	10.1021/acs.jmedchem.8b01556
Abstrakt:	A deconstruction of previously reported phosphoinositide 3-kinase δ (PI3Kδ) inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3Kδ, which was exploited to deliver a potent, efficient, and selective lead series with a novel binding mode observed in the PI3Kδ crystal structure.
Databáze:	MEDLINE
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