4-((but-3-en-1-ylamino)methyl)benzonitrile | 1258215-68-7

• 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: 4-((but-3-en-1-ylamino)methyl)benzonitrile
• 英文别名: 4-[(But-3-enylamino)methyl]benzonitrile
• CAS: 1258215-68-7
• 化学式: C₁₂H₁₄N₂
• 分子量: 186.257
• InChiKey: KWLNKVAEQHQBBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-((but-3-en-1-ylamino)methyl)benzonitrile 在 Grubbs catalyst first generation 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 3-(1-(4-cyanobenzyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanoate
  参考文献：
  名称：

  Property based optimization of δ-lactam HDAC inhibitors for metabolic stability

  摘要：

  The novel delta-lactam based HDAC inhibitor, KBH-A118 (3) shows a good HDAC enzyme and cancer cell growth inhibitory activities but has undesirable pharmacokinetics profiles because of instability in mouse liver microsome. To improve metabolic stability, various analogues were prepared with substituents on aromatic ring of cap group and various chain lengths between the cap group and delta-lactam core. The newly prepared analogues showed moderate to potent in vitro activities. Among them six compounds (8a, 8e, 8j, 8n, 8t, and 8v) were evaluated on mouse liver microsome assay and it turned out that the microsomal stabilities were dependent on lipophilicity and the number of the rotatable bonds. Finally, the animal pharmacokinetic profiles of 8e displayed improving oral exposure and oral bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.117
• 作为产物：
  描述：

  对氰基苄胺 、 4-溴-1-丁烯 在 sodium iodide 作用下， 以 乙醇 为溶剂， 以50 %的产率得到4-((but-3-en-1-ylamino)methyl)benzonitrile
  参考文献：
  名称：

  可见光驱动的多组分反应，用于通过自由基硫代氨基甲酰化多功能合成硫代酰胺

  摘要：

  提出了一系列可见光驱动的胺、二硫化碳和烯烃的多组分反应，用于线性硫代酰胺和环状硫代内酰胺的温和且通用的合成。使用廉价且容易获得的二硫化碳作为自由基途径中的硫代羰基源，使得结构多样的胺部分与非亲核碳基反应伙伴能够轻松组装。

  DOI：

  10.1002/anie.202409605

文献信息

• Lactam-Based HDAC Inhibitors for Anticancer Chemotherapy: Restoration of RUNX3 by Posttranslational Modification and Epigenetic Control
  作者：Misun Cho、Eunhyun Choi、Jae Hyun Kim、Hwan Kim、Hwan Mook Kim、Jang Ik Lee、Ki-Chul Hwang、Hyun-Jung Kim、Gyoonhee Han

  DOI：10.1002/cmdc.201300393

  日期：2014.3

  transcription factor 3 (RUNX3) are regulated by histone deacetylase (HDAC). HDAC inhibition alters epigenetic and posttranslational stability of RUNX3, leading to tumor suppression. However, HDAC inhibitors can nonselectively alter global gene expression through chromatin remodeling. Thus, lactam‐based HDAC inhibitors were screened to identify potent protein stabilizers that maintain RUNX3 stability by acetylation

  肿瘤抑制子相关转录因子3（RUNX3）的表达和稳定性受组蛋白脱乙酰基酶（HDAC）调节。HDAC抑制会改变RUNX3的表观遗传和翻译后稳定性，从而导致肿瘤抑制。但是，HDAC抑制剂可以通过染色质重塑非选择性地改变全局基因的表达。因此，筛选了基于内酰胺的HDAC抑制剂以鉴定有效的蛋白质稳定剂，该稳定剂可通过乙酰化保持RUNX3的稳定性。通过基于细胞的RUNX激活和HDAC抑制测定法确定了111种基于内酰胺的类似物的RUNX活性和HDAC抑制作用。3- [1-（4-溴苄基）-2-氧代-2,5-二氢-1 H-吡咯-3-基] -N-羟基丙酰胺（11-8）可显着提高RUNX3的乙酰化和稳定性，并具有相对较低的RUNX3 mRNA表达和HDAC抑制活性。在MKN28异种移植模型中，该化合物显示出显着的抗肿瘤作用，比SAHA强。因此，我们提出了一种新的策略，其中HDAC抑制剂用作选择性靶向RUNX3的表
• Property based optimization of δ-lactam HDAC inhibitors for metabolic stability
  作者：Hong Chul Yoon、Eunhyun Choi、Jung Eun Park、Misun Cho、Jeong Jea Seo、Soo Jin Oh、Jong Soon Kang、Hwan Mook Kim、Song-Kyu Park、Kiho Lee、Gyoonhee Han

  DOI：10.1016/j.bmcl.2010.08.117

  日期：2010.11

  The novel delta-lactam based HDAC inhibitor, KBH-A118 (3) shows a good HDAC enzyme and cancer cell growth inhibitory activities but has undesirable pharmacokinetics profiles because of instability in mouse liver microsome. To improve metabolic stability, various analogues were prepared with substituents on aromatic ring of cap group and various chain lengths between the cap group and delta-lactam core. The newly prepared analogues showed moderate to potent in vitro activities. Among them six compounds (8a, 8e, 8j, 8n, 8t, and 8v) were evaluated on mouse liver microsome assay and it turned out that the microsomal stabilities were dependent on lipophilicity and the number of the rotatable bonds. Finally, the animal pharmacokinetic profiles of 8e displayed improving oral exposure and oral bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.