(S,E)-methyl 3-(3-(6-bromopyridin-2-yl)-2-cyanoacrylamido)-3-phenylpropanoate | 1001088-65-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S,E)-methyl 3-(3-(6-bromopyridin-2-yl)-2-cyanoacrylamido)-3-phenylpropanoate
• 英文别名: methyl (3S)-3-[[(E)-3-(6-bromopyridin-2-yl)-2-cyanoprop-2-enoyl]amino]-3-phenylpropanoate
• CAS: 1001088-65-8
• 化学式: C₁₉H₁₆BrN₃O₃
• 分子量: 414.258
• InChiKey: CQJCYXYDSUGERD-DKGMDFAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-3-氨基-3-苯基丙酸甲酯 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 (S,E)-methyl 3-(3-(6-bromopyridin-2-yl)-2-cyanoacrylamido)-3-phenylpropanoate
  参考文献：
  名称：

  Tyrphostin-like compounds with ubiquitin modulatory activity as possible therapeutic agents for multiple myeloma

  摘要：

  With the goal of developing small molecules as novel regulators of signal transduction and apoptosis, a series of tyrphostin-like compounds were synthesized and screened for their activity against MM-1 (multiple myeloma) cells and other cell lines representing this malignancy. Synthesis was completed in solution-phase initially and then adopted to solid-phase for generating a more diverse set of compounds. A positive correlation was noted between compounds capable of inducing apoptosis and their modulation of protein ubiquitination. Further analysis suggested that ubiquitin modulation occurs through inhibition of cellular deubiquitinase activity. Bulky groups on the sidechain near the alpha,beta-unsaturated ketone caused a complete loss of activity, whereas cyclization on the opposite side was tolerated. Theoretical calculations at the B3LYP/LACV3P** level were completed on each molecule, and the resulting molecular orbitals and Fukui reactivity values for C(beta) carbon were utilized in developing a model to explain the compound activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.057

文献信息

• TRYPHOSTIN-ANALOGS FOR THE TREATMENT OF CELL PROLIFERATIVE DISEASES
  申请人：Donato Nicholas J

  公开号：US20100292229A1

  公开（公告）日：2010-11-18

  The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. In general aspects, compounds of the present invention are tyrphostin-like in structure. Compounds of the present invention, in certain embodiments, display significant potency by causing, for example, inhibition of Stat3 activation, reduction in c-myc protein levels and/or induction of apoptosis in tumor cells. In general aspects, compounds of the present invention induce one or more of these activities at nanomolar concentrations and typically function through a unique mechanism involving the induction of stress granules that bind specific signaling molecules and prevent them from participating in signal transduction and oncogenesis.

  本发明涉及化合物及其用于治疗细胞增殖性疾病，如癌症。在一般方面，本发明的化合物在结构上类似于酪氨酸激酶抑制剂。在某些实施例中，本发明的化合物通过诱导应激颗粒结合特定信号分子并阻止它们参与信号转导和肿瘤发生，从而表现出显著的效力，例如抑制Stat3激活、降低c-myc蛋白水平和/或诱导肿瘤细胞凋亡。在一般方面，本发明的化合物在纳摩尔浓度下诱导这些活性中的一个或多个，并通常通过诱导应激颗粒的独特机制发挥作用，这些应激颗粒结合特定信号分子并防止它们参与信号转导和肿瘤发生。