N-hydroxy-3-(1-(2-(naphthalen-2-yl)ethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propionamide | 959931-03-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-hydroxy-3-(1-(2-(naphthalen-2-yl)ethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propionamide
• 英文别名: N-hydroxy-3-(1-(2-(naphthalen-2-yl)ethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanamide；N-hydroxy-3-[1-(2-naphthalen-2-ylethyl)-6-oxo-2,3-dihydropyridin-5-yl]propanamide
• CAS: 959931-03-4
• 化学式: C₂₀H₂₂N₂O₃
• 分子量: 338.406
• InChiKey: BCTKRMDISVXKHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-萘-2-乙胺 在 Grubbs catalyst first generation 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 生成 N-hydroxy-3-(1-(2-(naphthalen-2-yl)ethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propionamide
  参考文献：
  名称：

  Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

  摘要：

  Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.034

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.
• Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors
  作者：Hwan Mook Kim、Sung Hee Hong、Myung Sook Kim、Chang Woo Lee、Jong Soon Kang、Kiho Lee、Song-Kyu Park、Jeung Whan Han、Hee Yoon Lee、Yongseok Choi、Ho Jeung Kwon、Gyoonhee Han

  DOI：10.1016/j.bmcl.2007.09.034

  日期：2007.11

  Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities. (C) 2007 Elsevier Ltd. All rights reserved.