(S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3yl)propoxy)phenyl)acrylate | 1526901-52-9

• 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-3yl)propoxy)phenyl)acrylate
• 英文别名: methyl (E)-3-[4-[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propoxy]phenyl]prop-2-enoate
• CAS: 1526901-52-9
• 化学式: C₂₆H₃₀N₂O₅
• 分子量: 450.535
• InChiKey: KOIJKGHWUAIZNI-IXDOJHRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3yl)propoxy)phenyl)acrylate 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.5h， 生成 (S,E)-methyl 3-(4-(2-([1,1′-biphenyl]-4-ylcarboxamido)-3-(1H-indol-3yl)propoxy)phenyl)acrylate
  参考文献：
  名称：

  Discovery of the First N-Hydroxycinnamamide-Based Histone Deacetylase 1/3 Dual Inhibitors with Potent Oral Antitumor Activity

  摘要：

  In our previous study, we designed and synthesized a novel series of N-hydroxycinnamamide-based HDAC inhibitors (HDACIs), among which the representative compound 14a exhibited promising HDACs inhibition and antitumor activity. In this current study, we report the development of a more potent class of N-hydroxycinnamamide-based HDACIs, using 14a as lead, among which, compound 11r gave IC50 values of 11.8, 498.1, 3.9, 2000.8, 5700.4, 308.2, and 900.4 nM for the inhibition of HDAC1, HDAC2, HDAC3, HDAC8, HDAC4, HDAC6, and HDAC11, exhibiting dual HDAC1/3 selectivity. Compounds 11e, 11r, 11w, and 11y showed excellent growth inhibition in multiple tumor cell lines. In vivo antitumor assay in U937 xenograft model identified compound 11r as a potent, orally active HDACI. To the best of our knowledge, this work constitutes the first report of oral active N-hydroxycinnamamide-based HDACIs with dual HDAC1/3 selectivity.

  DOI：

  10.1021/jm401877m
• 作为产物：
  描述：

  L-色氨酸 在 lithium aluminium tetrahydride 、 三乙胺 、 乙酰氯 、 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 4.0h， 生成 (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3yl)propoxy)phenyl)acrylate
  参考文献：
  名称：

  Discovery of the First N-Hydroxycinnamamide-Based Histone Deacetylase 1/3 Dual Inhibitors with Potent Oral Antitumor Activity

  摘要：

  In our previous study, we designed and synthesized a novel series of N-hydroxycinnamamide-based HDAC inhibitors (HDACIs), among which the representative compound 14a exhibited promising HDACs inhibition and antitumor activity. In this current study, we report the development of a more potent class of N-hydroxycinnamamide-based HDACIs, using 14a as lead, among which, compound 11r gave IC50 values of 11.8, 498.1, 3.9, 2000.8, 5700.4, 308.2, and 900.4 nM for the inhibition of HDAC1, HDAC2, HDAC3, HDAC8, HDAC4, HDAC6, and HDAC11, exhibiting dual HDAC1/3 selectivity. Compounds 11e, 11r, 11w, and 11y showed excellent growth inhibition in multiple tumor cell lines. In vivo antitumor assay in U937 xenograft model identified compound 11r as a potent, orally active HDACI. To the best of our knowledge, this work constitutes the first report of oral active N-hydroxycinnamamide-based HDACIs with dual HDAC1/3 selectivity.

  DOI：

  10.1021/jm401877m