Discovery of 4‐(Piperazin‐1‐yl)‐7H‐pyrrolo[2, 3‐d]pyrimidine Derivatives as Akt Inhibitors. Issue 5 (18th March 2016)

• Record Type: Journal Article
• Authors: Liu, Yang; Yin, Yanzhen; Zhang, Jingya; Nomie, Krystle; Zhang, Liang; Yang, Dezhi; Wang, Michael L.; Zhao, Guisen
• Is Part Of: Archiv der Pharmazie. Volume 349:Issue 5(2016)
• Page Start: 356
• Page End: 362
• Publication Date: 2016-03-18
• Subjects: Akt -- Anticancer -- Docking -- Pyrrolopyrimidines; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201500427
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : A series of 4‐(piperazin‐1‐yl)‐7 H ‐pyrrolo[2, 3‐d]pyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead (1 ). Typically, compounds5q and5t 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 inhibitors5q and5t might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents. Abstract : A series of pyrrolopyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead. Two compounds, 5q and5t, significantly improved the Akt1 inhibitory potency and antiproliferative effect against the cell lines LNCaP and PC‐3, suggesting that they might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents.