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磷脂酰肌醇3-激酶抑制剂ZSTK474的磺酰胺类似物的合成及生物学评价

Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474.

作者信息

Gamage Swarna A, Giddens Anna C, Tsang Kit Y, Flanagan Jack U, Kendall Jackie D, Lee Woo-Jeong, Baguley Bruce C, Buchanan Christina M, Jamieson Stephen M F, Shepherd Peter R, Denny William A, Rewcastle Gordon W

机构信息

Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

出版信息

Bioorg Med Chem. 2017 Oct 15;25(20):5859-5874. doi: 10.1016/j.bmc.2017.09.025. Epub 2017 Sep 20.

DOI:10.1016/j.bmc.2017.09.025
PMID:28958845
Abstract

Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise.

摘要

用含磺酰胺取代基替换磷脂酰肌醇3激酶（PI3K）抑制剂ZSTK474（1）的吗啉基团之一，产生了一类新型的活性和强效PI3Kα抑制剂。溶解性问题使得除6-氨基衍生物17外的所有化合物都无法进行体内评估，但该化合物的明显活性表明这类PI3K抑制剂具有很大的前景。

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