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Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant.

ABSTRACT: A series of AKT inhibitors possessing a piperidin-4-yl side chain was designed and synthesized. Some of them showed high AKT1 inhibitory activity and potent anti-proliferative effect on PC-3 prostate cancer cells in the preliminary screening. Further studies revealed the most potent compound, 10h, as a pan-AKT inhibitor. Compound 10h was able to inhibit the cellular phosphorylation of AKT effectively and induce apoptosis of PC-3 cells. It also showed high metabolic stability in human liver microsomes. Preclinical characterization of 10h, a promising lead AKT inhibitor, as a potential anti-prostate cancer therapeutic needs to be further investigated.

SUBMITTER: Zhang D

PROVIDER: S-EPMC6097228 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant.

Zhang Daoguang D Tong Dongdong D Yang Dezhi D Sun Jing J Zhang Fenghe F Zhao Guisen G

MedChemComm 20180703 8

A series of AKT inhibitors possessing a piperidin-4-yl side chain was designed and synthesized. Some of them showed high AKT1 inhibitory activity and potent anti-proliferative effect on PC-3 prostate cancer cells in the preliminary screening. Further studies revealed the most potent compound, <b>10h</b>, as a pan-AKT inhibitor. Compound <b>10h</b> was able to inhibit the cellular phosphorylation of AKT effectively and induce apoptosis of PC-3 cells. It also showed high metabolic stability in hum ...[more]

PMID: 30151089

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