[(R)-1-oxo-7-(pyridin-3-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-3-ylmethyl]-carbamic acid tert-butyl ester | 916454-45-0

• 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: [(R)-1-oxo-7-(pyridin-3-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-3-ylmethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[[(3R)-1-oxo-7-(pyridin-3-ylcarbamoyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-3-yl]methyl]carbamate
• CAS: 916454-45-0
• 化学式: C₂₃H₂₅N₅O₄
• 分子量: 435.483
• InChiKey: NIMQRYRFJUKXCX-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(R)-1-oxo-7-(pyridin-3-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-3-ylmethyl]-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以92%的产率得到indole-based 6-membered lactam, (R)-4a
  参考文献：
  名称：

  Synthesis and SAR studies of indole-based MK2 inhibitors

  摘要：

  Chemistry has been developed to specifically functionalize two structurally similar classes of indole-based MK2 inhibitors at positions prompted by a combination of X-ray crystallographic and computer assisted drug design. A gain in molecular potency was obtained by introducing aminomethyl groups to the lactam rings of 6-arylcarbamoyl-tetrahydro-beta-carbolinone and 6-arylcarbamoyl-dihydropyrazino[1,2-a] indolone MK2 inhibitors. In addition, improvements in molecular potency were achieved by expansion of the lactam from a 6- to 7-membered ring leading to 7-arylcarbamoyl-tetrahydro-[1,4] diazepino[1,2-a]indolones. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.119
• 作为产物：
  描述：

  3-氨基吡啶 、 (R)-3-(tert-butoxycarbonylamino-methyl)-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 以64%的产率得到[(R)-1-oxo-7-(pyridin-3-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-3-ylmethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Anti-Cytokine Heterocyclic Compounds

  摘要：

  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。

  公开号：

  US20060276453A1

文献信息

• 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。
• US7790712B2
  申请人：——

  公开号：US7790712B2

  公开（公告）日：2010-09-07
• Synthesis and SAR studies of indole-based MK2 inhibitors
  作者：Zhaoming Xiong、Donghong Amy Gao、Derek A. Cogan、Daniel R. Goldberg、Ming-Hong Hao、Neil Moss、Edward Pack、Chris Pargellis、Donna Skow、Thomas Trieselmann、Brian Werneburg、Andre White

  DOI：10.1016/j.bmcl.2008.01.119

  日期：2008.3

  Chemistry has been developed to specifically functionalize two structurally similar classes of indole-based MK2 inhibitors at positions prompted by a combination of X-ray crystallographic and computer assisted drug design. A gain in molecular potency was obtained by introducing aminomethyl groups to the lactam rings of 6-arylcarbamoyl-tetrahydro-beta-carbolinone and 6-arylcarbamoyl-dihydropyrazino[1,2-a] indolone MK2 inhibitors. In addition, improvements in molecular potency were achieved by expansion of the lactam from a 6- to 7-membered ring leading to 7-arylcarbamoyl-tetrahydro-[1,4] diazepino[1,2-a]indolones. (C) 2008 Elsevier Ltd. All rights reserved.
• 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。