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

  • Arch Pharm (Weinheim). 2016 May;349(5):356-62. doi: 10.1002/ardp.201500427.
Yang Liu  1 ,  Yanzhen Yin  1 ,  Jingya Zhang  1 ,  Krystle Nomie  2 ,  Liang Zhang  2 ,  Dezhi Yang  1 ,  Michael L Wang  2 ,  Guisen Zhao  1
Affiliations
  • 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, P. R. China.
  • 2. The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
PMID: 26991997 DOI: 10.1002/ardp.201500427
Abstract

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.

Keywords
Akt; Anticancer; Docking; Pyrrolopyrimidines.
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