Discovery of 4-(Piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Akt Inhibitors

被引：8

作者：

Liu, Yang ^{[1
]}

Yin, Yanzhen ^{[1
]}

Zhang, Jingya ^{[1
]}

Nomie, Krystle ^{[2
]}

Zhang, Liang ^{[2
]}

Yang, Dezhi ^{[1
]}

Wang, Michael L. ^{[2
]}

Zhao, Guisen ^{[1
]}

机构：

[1] Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci, Jinan 250012, Shandong, Peoples R China

[2] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

来源：

ARCHIV DER PHARMAZIE | 2016年 / 349卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Akt; Anticancer; Docking; Pyrrolopyrimidines; BREAST-CANCER; AKT/PKB; PATHWAY; RESISTANCE; THERAPY; DRUG;

D O I：

10.1002/ardp.201500427

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead (1). Typically, compounds 5q and 5t significantly improved the Akt1 inhibitory potency with IC50 values of 18.0 and 21.3 nM, respectively, with desirable antiproliferative effect against the cell lines LNCaP and PC-3. The inhibitors 5q and 5t might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents.

引用

页码：356 / 362

页数：7

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