(E)-methyl 3-(4-((S)-2-((S)-2,6-bis((tert-butoxycarbonyl)amino)hexanamido)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate | 1419146-83-0

• 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: (E)-methyl 3-(4-((S)-2-((S)-2,6-bis((tert-butoxycarbonyl)amino)hexanamido)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate
• CAS: 1419146-83-0
• 化学式: C₃₈H₅₂N₄O₉
• 分子量: 708.852
• InChiKey: OWXVZQHGDJRVGH-YOBZRWSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.06
• 重原子数：
  51.0
• 可旋转键数：
  16.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  166.31
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (E)-methyl 3-(4-((S)-2-((S)-2,6-bis((tert-butoxycarbonyl)amino)hexanamido)-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37%的产率得到tert-butyl N-[(2S)-1-[[(2S)-1-[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]-2-methoxyphenoxy]-3-(1H-indol-3-yl)propan-2-yl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxohexan-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：

  (S,E)-methyl 3-(4-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propoxy)-3-methoxyphenyl)acrylate 、 N-alpha-叔丁氧羰基-L-赖氨酸 在 三乙胺 、 三氟乙酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.25h， 以75%的产率得到(E)-methyl 3-(4-((S)-2-((S)-2,6-bis((tert-butoxycarbonyl)amino)hexanamido)-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