(5R,11aS)-2-butyl-5-(3-hydroxyphenyl)-3-thioxo-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carbolin-1-one

• 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,11aS)-2-butyl-5-(3-hydroxyphenyl)-3-thioxo-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carbolin-1-one
• 英文别名: (5R,11aS)-2-butyl-5-(3-hydroxyphenyl)-3-thioxo-6H-1,2,3,5,11,11a-hexahydroimidazo[1,5-b]-β-carboline-1-one；(10R,15S)-13-butyl-10-(3-hydroxyphenyl)-12-sulfanylidene-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-14-one
• 化学式: C₂₃H₂₃N₃O₂S
• 分子量: 405.521
• InChiKey: WLGVJJQBZZKUBM-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 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：
  91.7
• 氢给体数：
  2
• 氢受体数：
  3

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,11aS)-2-butyl-5-(3-hydroxyphenyl)-3-thioxo-6H-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carbolin-1-one
  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

• Synthesis and biological evaluation of functionalised tetrahydro-β-carboline analogues as inhibitors of Toxoplasma gondii invasion
  作者：Jeffrey G. A. Walton、Stephen Patterson、Gu Liu、Jeralyn D. Haraldsen、Jonathan J. Hollick、Alexandra M. Z. Slawin、Gary E. Ward、Nicholas J. Westwood

  DOI：10.1039/b902319d

  日期：——

  Techniques for the identification of the protein target(s) of small molecules are proving very important following an increase in the use of phenotype-based screening in chemical biology and drug discovery. One approach, known as the yeast-3-hybrid approach, has shown considerable potential. A key factor in the success of this approach is the preparation of a complex molecule referred to as a chemical inducer of dimerisation (CID). The synthesis of two CIDs based on a bioactive tetrahydro-β-carboline core structure is reported and evidence presented that shows the CIDs are of utility in this approach. A series of chemo- and bioinformatic studies coupled with SAR development inspired the choice of CIDs.

  小分子蛋白靶标识别的技术在化学生物学和药物发现中，随着表型筛选的增加，变得非常重要。一种被称为酵母三杂交的研究方法显示出相当大的潜力。这种方法成功的一个关键因素是准备一种被称为化学诱导剂（二聚化诱导剂，CID）的复杂分子。报告了基于一种生物活性四氢-β-卡巴林核心结构合成的两种CID，并提供了证据表明这些CID在该方法中的有效性。一系列的化学和生物信息学研究以及SAR发展启发了CID的选择。
• Methyl 1-imidazolecarbodithioate as a thiocarbonyl transfer reagent: a facile one-pot, three-component synthesis of novel 2-substituted-5-aryl-1-oxo-3-thioxo-1,2,3,5,11,11a-hexahydro-6H-imidazo-[1,5-b]-β-carbolines
  作者：Balendu Singh、G.S.M. Sundaram、Nimesh C. Misra、Hiriyakkanavar Ila

  DOI：10.1016/j.tetlet.2008.11.008

  日期：2009.1

  An efficient one-pot, three-component synthesis of novel 2-substituted-5-aryl-1-oxo-3-thioxo-1,2,3,5,11,11a-hexahydro-6H-imidazo-[1,5-b]-beta-carbolines employing 1-aryl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylates, primary amines (or amino acid esters) and methyl 1-imidazolecarbodithioate as the thiocarbonyl transfer reagent is reported. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.