3-(tert-butyl)-5-((4-methylpiperazin-1-yl)methyl)aniline | 1041053-68-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(tert-butyl)-5-((4-methylpiperazin-1-yl)methyl)aniline
• 英文别名: 3-Tert-butyl-5-((4-methylpiperazin-1-yl)methyl)benzenamine；3-tert-butyl-5-[(4-methylpiperazin-1-yl)methyl]aniline
• CAS: 1041053-68-2
• 化学式: C₁₆H₂₇N₃
• 分子量: 261.41
• InChiKey: SAMIYCHGYUKIFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(tert-butyl)-5-((4-methylpiperazin-1-yl)methyl)aniline 、 3-((6-(4-((tert-butoxycarbonyl)amino)phenyl)imidazo[1,2-a] pyrazin-3-yl)ethynyl)-2-methylbenzoic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors

  摘要：

  A series of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides was designed and synthesized as new tropomyosin receptor kinases (Trks) inhibitors by utilizing a structure-guided optimization strategy. One of the most potent compounds 90 suppressed TrkA/B/C with IC50 values of 2.65, 10.47 and 2.95 nM, respectively. The compound dose-dependently inhibited brain-derived neurotrophic factor (BDNF)-mediated TrkB activation and suppressed migration and invasion of SH-SY5Y-TrkB neuroblastoma cells expressing high level of TrkB. Inhibitor 90 also inhibited the proliferation of SH-SY5Y-TrkB cells with an IC50 value of 58 nM, which was comparable to that of an US FDA recently approved drug LOXO-101. Compound 90 may serve as a new lead compound for further anti-cancer drug discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.064
• 作为产物：
  描述：

  tert-butyl 3-tert-butyl-5-((4-methylpiperazin-1-yl)methyl)phenylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 3-(tert-butyl)-5-((4-methylpiperazin-1-yl)methyl)aniline
  参考文献：
  名称：

  WO2008/89034

  摘要：

  公开号：

文献信息

• Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors
  作者：Zhen Wang、Yali Zhang、Sergio G. Bartual、Jinfeng Luo、Tingting Xu、Wenting Du、Qiuju Xun、Zhengchao Tu、Rolf A. Brekken、Xiaomei Ren、Alex N. Bullock、Guang Liang、Xiaoyun Lu、Ke Ding

  DOI：10.1021/acsmedchemlett.6b00497

  日期：2017.3.9

  Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively

  急性肺损伤（ALI）是严重肺部炎症的致命症状。Discoidin域受体1（DDR1）是消炎药发现的新潜在靶标。发现一种新的基于选择性四氢异喹啉-7-羧酰胺的DDR1抑制剂7ae可以紧密结合DDR1蛋白并有效抑制其激酶功能，其Kd值为2.2 nM，IC50值为6.6 nM。该化合物剂量依赖性地抑制了脂多糖（LPS）诱导的白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）在小鼠原发性腹膜巨噬细胞（MPM）中的释放。此外，7ae在LPS诱导的小鼠ALI模型中还显示出有希望的体内抗炎作用。据我们所知，这是第一个“概念证明”
• Structure-Based Optimization of the Third Generation Type II Macrocycle TRK Inhibitors with Improved Activity against Solvent-Front, xDFG, and Gatekeeper Mutations
  作者：Zuqin Wang、Jie Wang、Yongjin Wang、Shuang Xiang、Hengliang Zhou、Shukai Song、Xiaojuan Song、Zhengchao Tu、Yang Zhou、Ke Ding、Zhi-Min Zhang、Zhang Zhang、Xiaoyun Lu

  DOI：10.1021/acs.jmedchem.3c00899

  日期：2023.9.28
• [EN] CYTOKINE INHIBITORS<br/>[FR] INHIBITEURS DE CYTOKINE
  申请人：KEMIA INC

  公开号：WO2008089034A2

  公开（公告）日：2008-07-24

  [EN] The present invention provides low molecular weight compounds useful as cytokine inhibitors, and compositions thereof. In particular, compounds of the invention are useful as anti-inflammatory agents. There are further provided methods for the preparation of such agents and their use in preventing or treating conditions mediated by cytokines, such as for example arthritis, pain, cardiovascular disease and cancer.
  [FR] La présente invention concerne des composés de faible masse moléculaire utiles comme inhibiteurs de cytokine et des compositions de ceux-ci. En particulier, des composés de l'invention sont utiles comme agents anti-inflammatoires. Il est en outre proposé des procédés pour la préparation de tels agents et leur utilisation pour la prévention ou le traitement d'affections véhiculées par des cytokines, telles que par exemple l'arthrite, la douleur, la maladie cardiovasculaire et le cancer.
• WO2008/89034
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors
  作者：Shengyang Cui、Yongjin Wang、Yuting Wang、Xia Tang、Xiaomei Ren、Lei Zhang、Yong Xu、Zhang Zhang、Zhi-Min Zhang、Xiaoyun Lu、Ke Ding

  DOI：10.1016/j.ejmech.2019.06.064

  日期：2019.10

  A series of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides was designed and synthesized as new tropomyosin receptor kinases (Trks) inhibitors by utilizing a structure-guided optimization strategy. One of the most potent compounds 90 suppressed TrkA/B/C with IC50 values of 2.65, 10.47 and 2.95 nM, respectively. The compound dose-dependently inhibited brain-derived neurotrophic factor (BDNF)-mediated TrkB activation and suppressed migration and invasion of SH-SY5Y-TrkB neuroblastoma cells expressing high level of TrkB. Inhibitor 90 also inhibited the proliferation of SH-SY5Y-TrkB cells with an IC50 value of 58 nM, which was comparable to that of an US FDA recently approved drug LOXO-101. Compound 90 may serve as a new lead compound for further anti-cancer drug discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.