- A nitrogen-containing heterocyclic phenyl piperidine compound and its preparation method and application
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The invention discloses a nitrogen-containing heterocyclic phenyl piperidine compound or pharmaceutical salt thereof. The general structural formula a of the compound is as shown in specification, wherein R represents hydrogen, mono-substituted or poly-substituted halogen, methyl, methoxyl, tertiary butyl or trifluoromethyl; and R2 is hydrogen, chlorine, bromine, methyl or ethyl. The compound disclosed by the invention is novel in structure; and by introducing the active amino in the form of a piperidine ring, the configuration of the side-chain amino is reinforced and the rigidity of the compound is enhanced. Through the design transformation, the Akt1 kinase inhibitory activity and the PC-3 cell line growth inhibitory activity of the compound are significantly enhanced.
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Paragraph 0075-0078; 0081
(2017/09/01)
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- Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity
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Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Akt1. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells. Low micromolar doses of 10h induced cell apoptosis and cell cycle arrest in G2/M phase, and significantly downregulated the phosphorylation of Akt downstream effectors GSK3β and S6 in Jeko-1 cells.
- Liu, Yang,Yin, Yanzhen,Zhang, Zhen,Li, Carrie J.,Zhang, Hui,Zhang, Daoguang,Jiang, Changying,Nomie, Krystle,Zhang, Liang,Wang, Michael L.,Zhao, Guisen
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p. 543 - 551
(2017/07/12)
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