(5R,11aR)-2-butyl-5-phenyl-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carboline-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (5R,11aR)-2-butyl-5-phenyl-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carboline-1,3-dione
• 英文别名: (10R,15R)-13-butyl-10-phenyl-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione
• 化学式: C₂₃H₂₃N₃O₂
• 分子量: 373.455
• InChiKey: CMJNCJLLBQHMPJ-TZIWHRDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  D-色氨酸 在 硫酸 作用下， 以 二甲基亚砜 、 丙酮 为溶剂， 生成 (5R,11aR)-2-butyl-5-phenyl-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carboline-1,3-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5

  摘要：

  The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.027

文献信息

• The Discovery of Tadalafil:  A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1<i>H</i>-imidazo[1‘,5‘:1,6]pyrido[3,4-<i>b</i>]indole-1,3(2<i>H</i>)-dione Analogues
  作者：Alain Daugan、Pascal Grondin、Cécile Ruault、Anne-Charlotte Le Monnier de Gouville、Hervé Coste、Jorge Kirilovsky、François Hyafil、Richard Labaudinière

  DOI：10.1021/jm030056e

  日期：2003.10.1

  Starting from ethyl beta-carboline-3-carboxylate (beta-CCE), 1, a modest inhibitor of type 5 phosphodiesterase (PDE5), a series of functionalized tetrahydro-p-carboline derivatives has been identified as a novel chemical class of potent and selective PDE5 inhibitors. Optimization of the side chain on the hydantoin ring of initial lead compound 2 and of the aromatic ring on position 5 led to the identification of compound 6e, a highly potent and selective PDE5 inhibitor, with greater selectivity for PDE5 vs PDE1-4 than sildenafil. Compound 6e demonstrated a long-lasting and significant blood pressure lowering effect after iv administration in the spontaneously hypertensive rat model but showed only moderate oral in vivo efficacy.
• Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5
  作者：Nils Sunder-Plassmann、Vasiliki Sarli、Michael Gartner、Mathias Utz、Jeanette Seiler、Stefan Huemmer、Thomas U. Mayer、Thomas Surrey、Athanassios Giannis

  DOI：10.1016/j.bmc.2005.06.027

  日期：2005.11

  The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.