4,4-dimethyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid ethyl ester | 916454-31-4

• 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: 4,4-dimethyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid ethyl ester
• 英文别名: ethyl 4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylate；ethyl 4,4-dimethyl-1-oxo-2,3-dihydropyrazino[1,2-a]indole-7-carboxylate
• CAS: 916454-31-4
• 化学式: C₁₆H₁₈N₂O₃
• 分子量: 286.331
• InChiKey: RMCPRNCWEJPSOP-UHFFFAOYSA-N

物化性质

• 沸点：
  520.4±38.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,4-dimethyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid ethyl ester 在 水 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.17h， 生成 4-{[(4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indol-7-yl)carbonyl]amino}-1-methyl-1H-imidazole-2-carboxylic acid
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE
  [FR] COMPOSÉS HÉTÉROCYCLIQUES CONTENANT UN COEUR INDOLE

  摘要：

  公开了抑制RSK的新颖化合物，制造此类化合物的方法以及包含此类化合物的药物组合物。还公开了使用本发明的化合物治疗RSK2调控失调的方法。

  公开号：

  WO2011071716A1
• 作为产物：
  描述：

  diethyl 1-(2-cyanopropan-2-yl)-1H-indole-2,6-dicarboxylate 在 镍 氢气 作用下， 以 水 为溶剂， 反应 18.0h， 以to afford the title compound (7.7 g, 95%) as a white solid的产率得到4,4-dimethyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid ethyl ester
  参考文献：
  名称：

  Heterocyclic compounds containing an indole core

  摘要：

  本发明涉及一种新型化合物，其可以抑制RSK，并且涉及制备这种化合物的方法以及包含这种化合物的制药组合物。本发明还涉及使用本发明的化合物治疗RSK2调节的疾病的方法。

  公开号：

  US09150577B2

文献信息

• Anti-Cytokine Heterocyclic Compounds
  申请人：Goldberg Daniel

  公开号：US20060276453A1

  公开（公告）日：2006-12-07

  Heterocyclic compounds and analogues thereof and their use as inhibitors of Mitogen-Activated Protein Kinase-Activated Protein kinase-2 (MAPKAP-k2), and also to a method for preventing or treating a disease or disorder that can be treated or prevented by modulating the activity of MAPKAP-K2 in a subject and to pharmaceutical compositions and kits that include these MAPKAP-K2 inhibitors.

  杂环化合物及其类似物以及它们作为丝裂原活化蛋白激酶激活蛋白激酶-2（MAPKAP-k2）抑制剂的用途，以及一种用于预防或治疗可以通过调节受试者中MAPKAP-K2活性来治疗或预防的疾病或紊乱的方法，以及包括这些MAPKAP-K2抑制剂的药物组合物和试剂盒。
• Substituted [1,4]diazepino[1,2-A]indoles and azepino[1,2-A]indoles as anti-cytokine inhibitors
  申请人：Boehringer Ingelheim Pharmaceutical, Inc.

  公开号：US07790712B2

  公开（公告）日：2010-09-07

  The application relates to compounds of formula Ia and analogues thereof wherein R1 to R13 and X are as defined herein. The invention also relates to the use of the compounds of formula Ia as inhibitors of Mitogen-Activated Protein Kinase-Activated Protein kinase-2 (MAPKAP-k2), and also to a method for preventing or treating a disease or disorder that can be treated or prevented by modulating the activity of MAPKAP-K2 in a subject and to pharmaceutical compositions and kits that include these MAPKAP-K2 inhibitors.

  本发明涉及公式Ia及其类似物的化合物，其中R1至R13和X的定义如本文所述。本发明还涉及将公式Ia化合物用作丝裂原活化蛋白激酶激活蛋白激酶2（MAPKAP-k2）的抑制剂，并涉及一种用于预防或治疗可以通过调节MAPKAP-K2活性来治疗或预防的疾病或障碍的方法，以及包括这些MAPKAP-K2抑制剂的制药组合物和试剂盒。
• HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE
  申请人：Boyer Stephen James

  公开号：US20130109679A1

  公开（公告）日：2013-05-02

  Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.

  本发明揭示了一种新型化合物，可抑制RSK，制备这种化合物的方法以及包含这种化合物的药物组合物。本发明还揭示了使用本发明化合物治疗RSK2调节的疾病的方法。
• Pyrazinoindolone inhibitors of MAPKAP-K2
  作者：D.R. Goldberg、Y. Choi、D. Cogan、M. Corson、R. DeLeon、A. Gao、L. Gruenbaum、M.H. Hao、D. Joseph、M.A. Kashem、C. Miller、N. Moss、M.R. Netherton、C.P. Pargellis、J. Pelletier、R. Sellati、D. Skow、C. Torcellini、Y.-C. Tseng、J. Wang、R. Wasti、B. Werneburg、J.P. Wu、Z. Xiong

  DOI：10.1016/j.bmcl.2007.12.037

  日期：2008.2

  Optimization of pyrazinoindolone inhibitors of MAPKAP-K2 (MK2) provides a reasonable balance of cellular potency and physicochemical properties. Mechanistic studies support the inhibition of MK2 which is responsible for the sub-micromolar cellular efficacy. (C) 2007 Elsevier Ltd. All rights reserved.
• Indole RSK inhibitors. Part 1: Discovery and initial SAR
  作者：Stephen J. Boyer、Jennifer Burke、Xin Guo、Thomas M. Kirrane、Roger J. Snow、Yunlong Zhang、Chris Sarko、Lida Soleymanzadeh、Alan Swinamer、John Westbrook、Frank DiCapua、Anil Padyana、Derek Cogan、Amy Gao、Zhaoming Xiong、Jeffrey B. Madwed、Mohammed Kashem、Stanley Kugler、Margaret M. O’Neill

  DOI：10.1016/j.bmcl.2011.10.030

  日期：2012.1

  A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were identified through high throughput screening. An RSK crystal structure and exploratory SAR were used to define the series pharmacophore. Compounds with good cell potency, such as compounds 43, 44, and 55 were identified, and form the basis for subsequent kinase selectivity optimization. (C) 2011 Elsevier Ltd. All rights reserved.