1-carboxymethyl-N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline | 1539289-73-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-carboxymethyl-N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline
• 英文别名: 2-[2-(2-Phenylacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]acetic acid；2-[2-(2-phenylacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]acetic acid
• CAS: 1539289-73-0
• 化学式: C₂₁H₂₀N₂O₃
• 分子量: 348.401
• InChiKey: ZDNJTXRSESMXRB-UHFFFAOYSA-N

物化性质

• 沸点：
  662.4±55.0 °C(predicted)
• 密度：
  1.320±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-methoxycarbonylmethyl-N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline 在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以68%的产率得到1-carboxymethyl-N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway

  摘要：

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.

  DOI：

  10.1021/jm401117t

文献信息

• Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway
  作者：Cong Zheng、Yuanzhang Fang、Weiguang Tong、Guoliang Li、Haigang Wu、Wenbo Zhou、Qingxiang Lin、Feifei Yang、Zhengfeng Yang、Peng Wang、Yangrui Peng、Xiufeng Pang、Zhengfang Yi、Jian Luo、Mingyao Liu、Yihua Chen

  DOI：10.1021/jm401117t

  日期：2014.2.13

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.