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带有哌啶-4-基侧链的AKT抑制剂的设计、合成及生物学评价

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

作者信息

Zhang Daoguang, Tong Dongdong, Yang Dezhi, Sun Jing, Zhang Fenghe, Zhao Guisen

机构信息

Department of Medicinal Chemistry , Key Laboratory of Chemical Biology (Ministry of Education) , School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong 250012 , PR China . Email:

Department of Oral and Maxillofacial Surgery , School of Stomatology , Shandong Provincial Key Laboratory of Oral Tissue Regeneration , Shandong University , Jinan , Shandong 250012 , PR China . Email:

出版信息

Medchemcomm. 2018 Jul 3;9(8):1340-1350. doi: 10.1039/c8md00197a. eCollection 2018 Aug 1.

DOI:10.1039/c8md00197a
PMID:30151089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6097228/
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, , as a pan-AKT inhibitor. Compound 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 , a promising lead AKT inhibitor, as a potential anti-prostate cancer therapeutic needs to be further investigated.

摘要

设计并合成了一系列具有哌啶-4-基侧链的AKT抑制剂。在初步筛选中，其中一些显示出高AKT1抑制活性以及对PC-3前列腺癌细胞的强效抗增殖作用。进一步研究表明，最有效的化合物 为一种泛AKT抑制剂。化合物 能够有效抑制AKT的细胞磷酸化并诱导PC-3细胞凋亡。它在人肝微粒体中也显示出高代谢稳定性。作为一种有前景的先导AKT抑制剂， 的临床前特性作为潜在的抗前列腺癌治疗药物有待进一步研究。

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本文引用的文献

1
Recent progress towards clinically relevant ATP-competitive Akt inhibitors.具有临床相关性的ATP竞争性Akt抑制剂的近期进展。
Bioorg Med Chem Lett. 2017 Jul 1;27(13):2838-2848. doi: 10.1016/j.bmcl.2017.04.090. Epub 2017 Apr 29.
2
AKT/PKB Signaling: Navigating the Network.AKT/蛋白激酶B信号传导：探索该网络
Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.
3
Discovery of 4-(Piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Akt Inhibitors.4-(哌嗪-1-基)-7H-吡咯并[2,3-d]嘧啶衍生物作为Akt抑制剂的发现
Arch Pharm (Weinheim). 2016 May;349(5):356-62. doi: 10.1002/ardp.201500427. Epub 2016 Mar 18.
4
PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate.醋酸阿比特龙治疗去势抵抗性前列腺癌时PTEN蛋白缺失与临床结局
Eur Urol. 2015 Apr;67(4):795-802. doi: 10.1016/j.eururo.2014.10.027. Epub 2014 Nov 4.
5
Structure-based design, synthesis and biological evaluation of diphenylmethylamine derivatives as novel Akt1 inhibitors.基于结构的新型 Akt1 抑制剂二苯甲胺衍生物的设计、合成与生物评价。
Eur J Med Chem. 2014 Feb 12;73:167-76. doi: 10.1016/j.ejmech.2013.11.036. Epub 2013 Dec 19.
6
Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases.发现 4-氨基-N-[(1S)-1-(4-氯苯基)-3-羟基丙基]-1-(7H-吡咯并[2,3-d]嘧啶-4-基)哌啶-4-甲酰胺（AZD5363），一种口服生物利用度高、有效的 Akt 激酶抑制剂。
J Med Chem. 2013 Mar 14;56(5):2059-73. doi: 10.1021/jm301762v. Epub 2013 Feb 26.
7
Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors.发现和临床前药理学研究一种选择性的 ATP 竞争型 Akt 抑制剂（GDC-0068），用于治疗人类肿瘤。
J Med Chem. 2012 Sep 27;55(18):8110-27. doi: 10.1021/jm301024w. Epub 2012 Sep 18.
8
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J Med Chem. 2008 Sep 25;51(18):5663-79. doi: 10.1021/jm8004527.
9
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J Med Chem. 2007 May 17;50(10):2289-92. doi: 10.1021/jm0700924. Epub 2007 Apr 24.
10
Identification of inhibitors of protein kinase B using fragment-based lead discovery.使用基于片段的先导化合物发现方法鉴定蛋白激酶B的抑制剂。
J Med Chem. 2007 May 17;50(10):2293-6. doi: 10.1021/jm070091b. Epub 2007 Apr 24.