8-methoxy-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one | 127556-77-8

• 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: 8-methoxy-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one
• 英文别名: 8-methoxy-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one
• CAS: 127556-77-8
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: FFBDMPJYUPKPSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  43.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-methoxy-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one 在 lithium aluminium tetrahydride 、 sodium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以96%的产率得到8-methoxy-1,2,3,4-tetrahydropyrazino<1,2-a>indole
  参考文献：
  名称：

  [a]-FUSED INDOLE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  该发明涉及Formula II的[a]-融合吲哚化合物，或其药用可接受的盐，其中组成变量如本文所定义。该发明还涉及包含Formula II化合物的组合物，以及制备和使用这些化合物的方法。

  公开号：

  US20090192147A1
• 作为产物：
  描述：

  5-甲氧基吲哚-2-甲酸乙酯 在 sodium tetrahydroborate 、 sodium hydride 、 cobalt(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 8-methoxy-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one
  参考文献：
  名称：

  吲哚并六氢吡嗪并喹唑啉酮类抗肿瘤化合物及 其制备方法

  摘要：

  本发明涉及医药技术领域，具体涉及一类吲哚并六氢吡嗪并喹唑啉酮类抗肿瘤化合物及其制备方法。本发明的吲哚并六氢吡嗪并喹唑啉酮类化合物，其化学结构式如通式I或通式II所示，该类化合物是通过对吴茱萸碱进行了系统的骨架跃迁设计与合成得到一类吴茱萸碱新骨架化合物，是新发现的一类全新结构的拓扑异构酶I/微管蛋白双重抑制剂，具有明显抗肿瘤活性。本发明还提供了该类化合物在制备拓扑异构酶I/微管蛋白双重抑制剂和抗肿瘤药物中的应用。

  公开号：

  CN103992326B

文献信息

• Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer
  作者：Lei Wang、Kun Fang、Junfei Cheng、Yu Li、Yahui Huang、Shuqiang Chen、Guoqiang Dong、Shanchao Wu、Chunquan Sheng

  DOI：10.1021/acs.jmedchem.9b01626

  日期：2020.1.23

  Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.
• Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands
  作者：Christian Markl、Mohamed I. Attia、Justin Julius、Shalini Sethi、Paula A. Witt-Enderby、Darius P. Zlotos

  DOI：10.1016/j.bmc.2009.04.068

  日期：2009.7

  Two novel series of melatonin-derived compounds have been synthesized and pharmacologically evaluated at the MT1 and MT2 subtypes of melatonin receptors. Compounds 12b-c are non-selective high-affinity MT1 and MT2 receptor ligands (K-i = 7-11 nM). Compound 12b had little intrinsic activity at the MT1 receptor and no intrinsic activity at the MT2 receptor. Compound 20d displayed the highest MT2 binding affinity (K-i = 2 nM) and moderate selectivity toward the MT2 subtype (K-i MT1/MT2 ratio = 8) behaving as MT2 antagonist and MT1 agonist (IC50 = 112 pM). The findings help define SARs around the positions 1 and 2 of melatonin with respect to binding affinity, MT2 selectivity, and intrinsic activity. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and pharmacological activity of 1-imino-1,2,3,4-tetrahydropyrazino[1,2-a]indolel derivatives
  作者：S. A. Zaitsev、R. G. Glushkov、M. D. Mashkovskii、N. I. Andreeva

  DOI：10.1007/bf00764807

  日期：1989.10
• ZAJTSEV, S. A.;GLUSHKOV, R. G.;MASHKOVSKIJ, M. D.;ANDREEVA, N. I., XIM.-FARMATS. ZH., 23,(1989) N0, S. 1201-1203
  作者：ZAJTSEV, S. A.、GLUSHKOV, R. G.、MASHKOVSKIJ, M. D.、ANDREEVA, N. I.

  DOI：——

  日期：——
• [EN] [A]-FUSED INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES<br/>[FR] COMPOSÉS D'INDOLE FONDUS-[A], LEUR UTILISATION EN TANT QU'INHIBITEURS DE MTOR KINASE ET DE PI3 KINASE, ET LEURS SYNTHÈSES
  申请人：WYETH CORP

  公开号：WO2009097515A2

  公开（公告）日：2009-08-06

  The invention relates to [a]-fused indole compounds of the Formula II, or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein. The invention also relates to compositions comprising the compounds of Formula II, and methods for making and using the compounds.