N-(2-morpholinoethyl)-1H-indol-6-amine | 1239447-41-6

• 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: N-(2-morpholinoethyl)-1H-indol-6-amine
• 英文别名: N-(2-morpholin-4-ylethyl)-1H-indol-6-amine
• CAS: 1239447-41-6
• 化学式: C₁₄H₁₉N₃O
• 分子量: 245.324
• InChiKey: CPOUHMDJDNWCRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  40.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-morpholinoethyl)-1H-indol-6-amine 、 右旋酮洛芬 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以58%的产率得到2-(3-benzoylphenyl)-N-(1H-indol-6-yl)-N-(2-morpholinoethyl)propanamide
  参考文献：
  名称：

  Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway

  摘要：

  We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory activity and membrane permeability, while also improving the microsome stability. Among them, 33 and 42 inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with Gli1 with 2.6 mu M and 1.6 mu M of IC50, respectively, and in Rh30 cells that endogenously over-express Gli1, and were selective to Gli1 over Gli2. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.001
• 作为产物：
  描述：

  6-氨基吲哚 、 N-(2-氯乙基)吗啉盐酸盐 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以50%的产率得到N-(2-morpholinoethyl)-1H-indol-6-amine
  参考文献：
  名称：

  Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway

  摘要：

  We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory activity and membrane permeability, while also improving the microsome stability. Among them, 33 and 42 inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with Gli1 with 2.6 mu M and 1.6 mu M of IC50, respectively, and in Rh30 cells that endogenously over-express Gli1, and were selective to Gli1 over Gli2. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.001

文献信息

• [EN] SUBSTITUTED ARYL-AMINE DERIVATIVES AND METHODS OF USE<br/>[FR] DÉRIVÉS AMINÉS À SUBSTITUTION ARYLE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2006012374A1

  公开（公告）日：2006-02-02

  The present invention provides classes of compounds, including-their pharmaceutically acceptable derivatives, useful for treating angiogenesis and related diseases such as cancer. Formula I and II wherein R is a 9- or 10-membered heterocyclyl ring selected from 7-isoquinolinyl,..2-methyl-3-oxo-2,3-dihydroindazol-6-yl, [1,6]-naphthydrin-3-yl, [1,7]-naphthydrin-2-yl, 1-oxo-2,3-dihydrobenzofuran-4-yl, 3-oxo-2,3-dihydrobenzofuran-5-yl, dihydro-benzodioxinyl, 6-quinazolinyl, 2-amino-6-quinazolinyl, 4-methylamino-6-quinazolinyl, 2,4-diamino-6 quinazolinyl, 3-oxo-3,4-dihydro-1,4-benzoxazin-6-yl, 2,2-difluoro-l;3-benzodioxol-5-yl and 2,2,3,3 tetrafluoro-2,3-dihydro-l,4-benzodioxin-6-yl, each of which is optionally substituted with one or more substituents selected from halo, haloakyl, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, N-dimethylamino-C1-6-alkyl, N-dimethylamino-C1-6-alkoxy, amino, alkyl-carbonylamino, morpholino-sulfonyl, amino-sulfonyl, oxazolyl, pyrrolyl,4 morpholinyl, carboxyl, cyano, and acetyl; wherein R1 in formula I is selected from unsubstituted or substituted phenyl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl and 11-14 membered tricyclic heterocyclyl, and R1 in formula II is selected from specific bicyclic heterocycles.

  本发明提供了一类化合物，包括其药用可接受的衍生物，用于治疗血管生成和相关疾病，如癌症。其中R为从7-异喹啉基、2-甲基-3-氧代-2,3-二氢吲哚-6-基、[1,6]-萘啶-3-基、[1,7]-萘啶-2-基、1-氧代-2,3-二氢苯并呋喃-4-基、3-氧代-2,3-二氢苯并呋喃-5-基、二氢苯并二氧杂环基、6-喹唑啉基、2-氨基-6-喹唑啉基、4-甲氨基-6-喹唑啉基、2,4-二氨基-6-喹唑啉基、3-氧代-3,4-二氢-1,4-苯并噁嗪-6-基、2,2-二氟-1,3-苯并二氧杂环-5-基和2,2,3,3-四氟-2,3-二氢-1,4-苯并二氧杂环-6-基中选择的9-或10-成员杂环基，其中每个基可选择地被一个或多个来自卤素、卤代烷基、C1-6烷基、C2-8烯基、C2-8炔基、N-二甲氨基-C1-6-烷基、N-二甲氨基-C1-6-烷氧基、氨基、烷基-羰基氨基、吗啉磺酰基、氨基磺酰基、噁唑基、吡咯基、吗啉基、羧基、氰基和乙酰基的取代基取代；其中式I中的R1从未取代或取代的苯基、5-6成员杂芳基、9-10成员双环杂环基和11-14成员三环杂环基中选择，式II中的R1从特定的双环杂环基中选择。
• SUBSTITUTED ARYL-AMINE DERIVATIVES AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：EP1773817A1

  公开（公告）日：2007-04-18
• Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway
  作者：Neeraj Mahindroo、Michele C. Connelly、Chandanamali Punchihewa、Lei Yang、Bing Yan、Naoaki Fujii

  DOI：10.1016/j.bmc.2010.05.001

  日期：2010.7

  We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory activity and membrane permeability, while also improving the microsome stability. Among them, 33 and 42 inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with Gli1 with 2.6 mu M and 1.6 mu M of IC50, respectively, and in Rh30 cells that endogenously over-express Gli1, and were selective to Gli1 over Gli2. (C) 2010 Elsevier Ltd. All rights reserved.