(S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate | 1403949-81-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate
• 英文别名: methyl (S,E)-3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate；methyl (E)-3-[4-[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propoxy]-3-methoxyphenyl]prop-2-enoate
• CAS: 1403949-81-4
• 化学式: C₂₇H₃₂N₂O₆
• 分子量: 480.561
• InChiKey: CFZRLSOGFBZVJW-RPAADVPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate 在 羟胺钾盐 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以51%的产率得到tert-butyl N-[(2S)-1-[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]-2-methoxyphenoxy]-3-(1H-indol-3-yl)propan-2-yl]carbamate
  参考文献：
  名称：

  Development of N-Hydroxycinnamamide-Based Histone Deacetylase Inhibitors with an Indole-Containing Cap Group

  摘要：

  A novel series of histone deacetylase inhibitors combining N-hydroxycinnamamide bioactive fragment and indole bioactive fragment was designed and synthesized. Several compounds (17c, 17g, 17h, 17j, and 17k) exhibited comparable, even superior, total HDACs inhibitory activity and in vitro antiproliferative activities relative to the approved drug SAHA. A representative compound 17a with moderate HDACs inhibition was progressed to isoform selectivity profile, Western blot analysis, and in vivo antitumor assay. Although HDACs isoform selectivity of 17a was similar to that of SAHA, our Western blot results indicated that intracellular effects of 17a at 1 mu M were class I selective. It was noteworthy that the effect on histone H4 acetylation of SAHA decreased with time, while the effect on histone H4 acetylation of 17a was maintained and even increased. Most importantly, compound 17a exhibited promising in vivo antitumor activity in a U937 xenograft model.

  DOI：

  10.1021/ml300366t
• 作为产物：
  描述：

  L-色氨酸 在 lithium aluminium tetrahydride 、 氯化亚砜 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate
  参考文献：
  名称：

  Development of N-Hydroxycinnamamide-Based Histone Deacetylase Inhibitors with an Indole-Containing Cap Group

  摘要：

  A novel series of histone deacetylase inhibitors combining N-hydroxycinnamamide bioactive fragment and indole bioactive fragment was designed and synthesized. Several compounds (17c, 17g, 17h, 17j, and 17k) exhibited comparable, even superior, total HDACs inhibitory activity and in vitro antiproliferative activities relative to the approved drug SAHA. A representative compound 17a with moderate HDACs inhibition was progressed to isoform selectivity profile, Western blot analysis, and in vivo antitumor assay. Although HDACs isoform selectivity of 17a was similar to that of SAHA, our Western blot results indicated that intracellular effects of 17a at 1 mu M were class I selective. It was noteworthy that the effect on histone H4 acetylation of SAHA decreased with time, while the effect on histone H4 acetylation of 17a was maintained and even increased. Most importantly, compound 17a exhibited promising in vivo antitumor activity in a U937 xenograft model.

  DOI：

  10.1021/ml300366t

文献信息

• Development of N -hydroxycinnamamide-based HDAC inhibitors with improved HDAC inhibitory activity and in vitro antitumor activity
  作者：Jie Zang、Baowen Shi、Xuewu Liang、Qianwen Gao、Wenfang Xu、Yingjie Zhang

  DOI：10.1016/j.bmc.2016.12.001

  日期：2017.5

  deacetylases (HDACs) inhibitory activity than their parent compound 1 and even the positive control SAHA. What's more, compared with the approved HDACs inhibitor SAHA, compounds 6i, 6k, 6q and 6t displayed better in vitro antiproliferation against multiple tumor cell lines. It is worth noting that though the 4-hydroxycinnamic acid-based compound 2 showed HDAC1/3 dual selectivity, its 4-hydroxy-3-methoxycinnamic

  组蛋白脱乙酰基酶抑制剂（HDACIs）在治疗各种疾病方面很有前途，其中癌症治疗取得了最大的成功。我们以前已经开发了一系列结合N-羟基肉桂酰胺生物活性片段和吲哚生物活性片段的HDACI，它们显示出中等至有效的抗肿瘤活性。在此，根据我们先前的结构-活性关系（SAR），进一步的结构衍生化得到了25种新化合物。大多数化合物显示出比其母体化合物1甚至阳性对照SAHA更有效的组蛋白脱乙酰基酶（HDAC）抑制活性。而且，与批准的HDACs抑制剂SAHA相比，化合物6i，6k，6q和6t对多种肿瘤细胞系表现出更好的体外抗增殖作用。