4-(2-氨基-1-(4-(三氟甲基)苯基)乙基)哌嗪-1-羧酸叔丁酯 | 444892-59-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(2-氨基-1-(4-(三氟甲基)苯基)乙基)哌嗪-1-羧酸叔丁酯
• 英文名称: 4-[2-amino-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-(2-amino-1-(4-(trifluoromethyl)phenyl)ethyl)piperazine-1-carboxylate；tert-butyl 4-[2-amino-1-[4-(trifluoromethyl)phenyl]ethyl]piperazine-1-carboxylate
• CAS: 444892-59-5
• 化学式: C₁₈H₂₆F₃N₃O₂
• 分子量: 373.419
• InChiKey: HAMPKJFJUJORMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(2-氨基-1-(4-(三氟甲基)苯基)乙基)哌嗪-1-羧酸叔丁酯 在 吡啶 、 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 N-[2-{4-[3-(4-Bromo-phenoxy)-2-hydroxy-propyl]-piperazin-1-yl}-2-(4-trifluoromethyl-phenyl)-ethyl]-3-methyl-benzenesulfonamide
  参考文献：
  名称：

  The design, preparation and SAR of novel small molecule sodium (Na + ) channel blockers

  摘要：

  A parallel strategy incorporating predictive modeling of both sodium site 2 blocking activity and cytochrome P450 CYP2D6 enzyme activity as well as experimental data from ADME profiling (eADME) has been applied to the design of new small molecule sodium channel blockers. New structural motifs were identified, which combined sodium channel activity with decreased ADME liabilities. Compounds 10h (site 2, IC50=531 nM) and 7j (site 2, IC50=149 nM) were identified from two structural classes as sodium channel blockers with favorable in vitro eADME profiles. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.078
• 作为产物：
  描述：

  对三氟甲基苯甲醛 在 lithium aluminium tetrahydride 、 zinc(II) iodide 作用下， 生成 4-(2-氨基-1-(4-(三氟甲基)苯基)乙基)哌嗪-1-羧酸叔丁酯
  参考文献：
  名称：

  Privileged structure based ligands for melanocortin receptors—Substituted benzylic piperazine derivatives

  摘要：

  Replacement of the aryl piperazine moiety in compound I with a variety of substituted benzylic piperazines (6) yields compounds that afford melanocortin receptor 4 (MCR4) activity. Analogs with ortho substitution on the aromatic ring afforded the highest affinity. Resolution of the stereocenter of the benzylic piperazine based privileged structure revealed that the R-enantiomer was more active. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.018

文献信息

• [EN] AMINOPYRIMIDINE DERIVATIVES FOR USE AS MODULATORS OF KINASE ACTIVITY<br/>[FR] DÉRIVÉS AMINOPYRIMIDINES À UTILISER EN TANT QUE MODULATEURS D'ACTIVITÉ KINASE
  申请人：MERCK PATENT GMBH

  公开号：WO2013040044A1

  公开（公告）日：2013-03-21

  The invention provides novel heterocyclic amine compounds accord¬ ing to Formula (I) and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

  这项发明提供了根据式（I）制备的新型杂环胺化合物，以及它们的制备和用于治疗高增殖性疾病，如癌症。
• Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors
  作者：Yufang Xiao、Bayard R. Huck、Ruoxi Lan、Lizbeth DeSelm、Xiaoling Chen、Hui Qiu、Constantin Neagu、Theresa Johnson、Igor Mochalkin、Anna Gardberg、Xuliang Jiang、Hui Tian、Vikram Dutt、Dusica Santos、Jared Head、Jennifer Jackson、Sakeena Syed、Jing Lin、Erik Wilker、Jianguo Ma、Anderson Clark、Andreas Machl、Donald Bankston、Christopher C.V. Jones、Andreas Goutopoulos、Brian Sherer

  DOI：10.1016/j.bmcl.2021.128352

  日期：2021.10

  PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K

  PI3K/Akt/mTOR 激酶通路的激活与人类癌症有关。双重 p70S6K/Akt 抑制剂足以抑制强烈的肿瘤生长并阻止补偿性 Akt 反馈回路激活的负面影响。基于现有喹唑啉甲酰胺系列的支架对接策略确定了 4-氨基嘧啶类似物6，其在 p70S6K 和 Akt 酶测定中显示出个位数的纳摩尔和微摩尔效力。SAR 优化提高了 Akt 酶和 p70S6K 细胞的效力，降低了 hERG 的敏感性，并最终发现了有希望的候选者37，它在 p70S6K 和 Akt 生化分析中都表现出个位数的纳摩尔值，以及 hERG 活性（IC 50 = 17.4 微米）。该药物在抑制小鼠乳腺癌肿瘤生长方面表现出剂量依赖性功效，并且在 200 mg/kg po 的剂量下长达 24 小时覆盖超过 90% 的 pS6 抑制。
• [EN] NOVEL HETEROCYCLIC DERIVATIVES AS MODULATORS OF KINASE ACTIVITY<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES COMME MODULATEURS DE L'ACTIVITÉ KINASE
  申请人：MERCK PATENT GMBH

  公开号：WO2014078637A1

  公开（公告）日：2014-05-22

  The invention provides novel imidazol-piperidinyl derivatives of the formula (I) in which R1, R2, W, X1, X2, X3, X4 and n have the meanings indicated in formula (I), and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

  该发明提供了公式（I）中的新型咪唑-哌啶衍生物，其中R1、R2、W、X1、X2、X3、X4和n具有公式（I）中所示的含义，并且它们的制造和用于治疗高增殖性疾病，如癌症。
• [EN] CALCILYTIC COMPOUNDS<br/>[FR] COMPOSÉS CALCILYTIQUE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010039911A1

  公开（公告）日：2010-04-08

  Novel calcilytic compounds, pharmaceutical compositions, methods of synthesis and methods of using them are provided.

  提供了新型钙受体拮抗剂化合物、药物组合物、合成方法和使用方法。
• AMINOPYRIMIDINE DERIVATIVES FOR USE AS MODULATORS OF KINASE ACTIVITY
  申请人：Lan Ruoxi

  公开号：US20150126484A1

  公开（公告）日：2015-05-07

  The invention provides novel heterocyclic amine compounds according to Formula (I) and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

  该发明提供了根据公式（I）的新型杂环胺化合物及其制备和用于治疗增殖过度性疾病，如癌症的用途。