4-((but-3-enyl)phenethylcarbamoyl)pent-4-enoic acid methyl ester | 905970-80-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-((but-3-enyl)phenethylcarbamoyl)pent-4-enoic acid methyl ester
• 英文别名: Methyl 4-[but-3-enyl(2-phenylethyl)carbamoyl]pent-4-enoate
• CAS: 905970-80-1
• 化学式: C₁₉H₂₅NO₃
• 分子量: 315.412
• InChiKey: DXUVFKJBFYUIJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((but-3-enyl)phenethylcarbamoyl)pent-4-enoic acid methyl ester 在 Grubbs catalyst first generation 、 羟胺钾盐 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 KBH-A40
  参考文献：
  名称：

  基于内酰胺的HDAC抑制剂用于抗癌化学疗法：通过翻译后修饰和表观遗传控制恢复RUNX3

  摘要：

  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

  DOI：

  10.1002/cmdc.201300393
• 作为产物：
  描述：

  2-亚甲基戊二酸 在 4-二甲氨基吡啶 、 camphor-10-sulfonic acid 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-((but-3-enyl)phenethylcarbamoyl)pent-4-enoic acid methyl ester
  参考文献：
  名称：

  Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel δ-lactam-based histone deacetylase (HDAC) inhibitors

  摘要：

  delta-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.091

文献信息

• Structure−Activity Relationship Studies of a Series of Novel δ-Lactam-Based Histone Deacetylase Inhibitors
  作者：Hwan Mook Kim、Dong-Kyu Ryu、Yongseok Choi、Bum Woo Park、Kiho Lee、Sang Bae Han、Chang-Woo Lee、Moo-Rim Kang、Jong Soon Kang、Shanthaveerappa K. Boovanahalli、Song-Kyu Park、Jung Whan Han、Tae-Gyu Chun、Hee-Yoon Lee、Ky-Youb Nam、Eun Hyun Choi、Gyoonhee Han

  DOI：10.1021/jm0613828

  日期：2007.5.1

  We synthesized a series of delta-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated anti-inflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-alpha and nitric oxide by LPS-stimulated RAW264.7 cells.
• Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel δ-lactam-based histone deacetylase (HDAC) inhibitors
  作者：Hwan Mook Kim、Kiho Lee、Bum Woo Park、Dong Kyu Ryu、Kangjeon Kim、Chang Woo Lee、Song-Kyu Park、Jung Whan Han、Hee Yoon Lee、Hyun Yong Lee、Gyoonhee Han

  DOI：10.1016/j.bmcl.2006.04.091

  日期：2006.8

  delta-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell. (c) 2006 Elsevier Ltd. All rights reserved.
• 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