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

被引：13

作者：

Giddens, Anna C. ^{[1
]}

Gamage, Swarna A. ^{[1
]}

Kendall, Jackie D. ^{[1
,2
]}

Lee, Woo-Jeong ^{[3
]}

Baguley, Bruce C. ^{[1
,2
]}

Buchanan, Christina M. ^{[2
,3
]}

Jamieson, Stephen M. F. ^{[1
,2
]}

Dickson, James M. J. ^{[2
,4
]}

Shepherd, Peter R. ^{[1
,2
,3
]}

Denny, William A. ^{[1
,2
]}

Rewcastle, Gordon W. ^{[1
,2
]}

机构：

[1] Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc, Res Ctr, Private Bag 92019, Auckland 1142, New Zealand

[2] Univ Auckland, Maurice Wilkins Ctr Mol Biodiscovery, Private Bag 92019, Auckland 1142, New Zealand

[3] Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Private Bag 92019, Auckland 1142, New Zealand

[4] Univ Auckland, Fac Sci, Sch Biol Sci, Private Bag 92019, Auckland 1142, New Zealand

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 08期

关键词：

Phosphatidylinositol; 3-kinase; PI3K; p110; alpha; ZSTK474; SN32976; PHOSPHOINOSITIDE; 3-KINASE; CLASS-I; PIK3CA GENE; PI3K; ISOFORM; PATHWAY; KINASE; MECHANISMS; P110-ALPHA; DISCOVERY;

D O I：

10.1016/j.bmc.2019.02.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Replacing one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 with a variety of sulfonamide-linked solubilizing substituents produced a new class of active and potent PI3K alpha inhibitors, with several derivatives demonstrating high PI3K alpha enzyme potency and good cellular potency in two human derived cell lines. The overall results suggest a preference for linear and somewhat flexible solubilizing functions. From this series, compound 16, also known as SN32976, was selected for advanced preclinical evaluation.

引用

页码：1529 / 1545

页数：17

共 44 条

[1] PIK3CA in cancer: The past 30 years [J].