tert-butyl (3S,4S)-3-amino-4-(4-chlorophenyl)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (3S,4S)-3-amino-4-(4-chlorophenyl)piperidine-1-carboxylate
• 英文别名: (3S,4S)-tert-butyl 3-amino-4-(4-chlorophenyl)piperidine-1-carboxylate
• 化学式: C₁₆H₂₃ClN₂O₂
• 分子量: 310.824
• InChiKey: SYHLKJDNDGXBIB-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,4S)-3-amino-4-(4-chlorophenyl)piperidine-1-carboxylate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 7.0h， 生成 4-bromo-N-((3S,4S)-4-(4-chlorophenyl)piperidin-3-yl)-5-(1-methyl-1H-pyrazol-5-yl)furan-2-carboxamide (2R,3R)-2,3-dihydroxysuccinate
  参考文献：
  名称：

  Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design

  摘要：

  A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, Al2, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure activity relationship of compound Al2, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Aktl and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.

  DOI：

  10.1021/acs.jmedchem.9b00891
• 作为产物：
  描述：

  氢溴酸槟榔碱 在 1-氯乙基氯甲酸酯 、 叠氮磷酸二苯酯 、 水 、 sodium methylate 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 13.58h， 生成 tert-butyl (3S,4S)-3-amino-4-(4-chlorophenyl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] CYCLIC AMINE AZAHETEROCYCLIC CARBOXAMIDES
  [FR] CARBOXAMIDES AZAHÉTÉROCYCLIQUES D'AMINES CYCLIQUES

  摘要：

  这项发明提供了根据式(I)、式(II)和式(III)制备的新型环胺氮杂杂环羧酰胺，以及它们用于治疗高增殖性疾病，如癌症的用途。

  公开号：

  WO2012016001A1

文献信息

• Discovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors
  作者：Wenhu Zhan、Jinxin Che、Lei Xu、Yizhe Wu、Xiaobei Hu、Yubo Zhou、Gang Cheng、Yongzhou Hu、Xiaowu Dong、Jia Li

  DOI：10.1016/j.ejmech.2019.07.017

  日期：2019.10

  A series of pyrazole-thiophene derivatives exhibiting good Akt inhibitory activities were obtained on the basis of conformational restriction strategy, leading to the discovery of compound 1d and 1o which showed excellent in vitro antitumor effect against a variety of hematologic cancer cells and their potential of inducing apoptosis, blocking the cell cycles at S phase and significantly inhibiting

  在构象限制策略的基础上，获得了一系列表现出良好的Akt抑制活性的吡唑-噻吩衍生物，从而发现了化合物1d和1o对多种血液癌细胞具有优异的体外抗肿瘤作用及其诱导潜力。凋亡，阻断S期的细胞周期，并显着抑制癌细胞Akt激酶下游生物标记的磷酸化。其中，化合物1o在MM1S异种移植模型中也表现出良好的PK特性，并抑制了约40％的肿瘤生长。化合物1o可能是进一步开发的潜在候选者。
• Cyclic Amine Azaheterocyclic Carboxamides
  申请人：Huck Bayard R.

  公开号：US20130217709A1

  公开（公告）日：2013-08-22

  The invention provides novel cyclic amine azaheterocyclic carboxamide according to Formula (I), Formula (II) and Formula (III) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

  该发明提供了新型的环状胺氮杂杂环羧酰胺，其化学式为(I)、(II)和(III)，以及它们的制造和用于治疗高增殖性疾病，如癌症的用途。
• Substituted nitrogen-containing heterocyclic derivatives, pharmaceutical compositions comprising the same and applications of antitumor thereof
  申请人：ZHEJIANG UNIVERSITY

  公开号：US10233180B2

  公开（公告）日：2019-03-19

  Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase.

  本发明公开了式(I)代表的作为AKT抑制剂的新取代含氮杂环衍生物、其光学异构体、药学上可接受的盐或溶液，其中R1、R2、R3、R4、R5、R6、环A、环C、B、Q、Y、Z和m的定义详见说明。此外，还公开了包含这些衍生物作为活性成分的药物，可用于治疗增殖性疾病，如癌症和炎症，尤其是与 AKT 激酶有关的疾病。
• SUBSTITUTED NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME AND APPLICATIONS OF ANTITUMOR THEREOF
  申请人：Zhejiang University

  公开号：EP3124486B1

  公开（公告）日：2020-12-09
• Discovery of Novel Oxazepine Derivatives as Akt/ROCK Inhibitors for Growth Arrest and Differentiation Induction in Neuroblastoma Treatment
  作者：Jinxin Che、Shaowei Bing、Jialiang Lu、Zegao Jin、Jian Gao、Haichao Sheng、Dan Li、Bo Yang、Qiaojun He、Meidan Ying、Xiaowu Dong

  DOI：10.1021/acs.jmedchem.3c00829

  日期：2023.10.12