Liu Yang, Yin Yanzhen, Zhang Jingya, Nomie Krystle, Zhang Liang, Yang Dezhi, Wang Michael L, Zhao Guisen
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, P. R. China.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Arch Pharm (Weinheim). 2016 May;349(5):356-62. doi: 10.1002/ardp.201500427. Epub 2016 Mar 18.
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.
通过优化一种弱筛选先导化合物（1），合成了一系列4-（哌嗪-1-基）-7H-吡咯并[2,3-d]嘧啶衍生物，并将其作为Akt抑制剂进行评估。通常，化合物5q和5t显著提高了Akt1抑制活性，IC50值分别为18.0和21.3 nM，对细胞系LNCaP和PC-3具有理想的抗增殖作用。抑制剂5q和5t可能作为先导化合物，用于进一步探索Akt抑制剂作为抗癌药物。
