4-cyano-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine | 1354454-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-cyano-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile
• CAS: 1354454-97-9
• 化学式: C₈H₇N₃
• 分子量: 145.164
• InChiKey: SGOXSUQAESDGFV-UHFFFAOYSA-N

物化性质

• 沸点：
  324.1±42.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyano-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine 、 (R)-3-(2-fluorophenoxy)-2-hydroxy-2-methylpropanoic acid 在 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 2.25h， 以8.5%的产率得到
  参考文献：
  名称：

  1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

  摘要：

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

  DOI：

  10.1021/jm401625b
• 作为产物：
  描述：

  4-氯-7-氮杂吲哚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 氢气 、 三乙胺 、 锌 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 140.0 ℃ 、344.75 kPa 条件下， 反应 26.5h， 生成 4-cyano-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Azaindolines: derisking the indoline structural alert

  摘要：

  4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrite 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.11.070

文献信息

• Structural and Computational Investigation of Intramolecular N···H Interactions in α‐ and β‐Fluorinated 7‐Azaindoline Amides
  作者：Lennart Brewitz、Hidetoshi Noda、Naoya Kumagai、Masakatsu Shibasaki

  DOI：10.1002/ejoc.201701083

  日期：2018.2.14

  and NMR spectroscopy: unusual intramolecular interactions between the 7-nitrogen and amide α-hydrogen atoms were identified. The strength of these interactions correlated with the electron-withdrawing character of the amide α-substituents. A combination of experimental and computational approaches revealed a significant substituent effect when the substituent (H, OMe, F, CN) was varied at the 4-position

  合成了新型氟化 N1-酰化 7-氮杂二氢吲哚，并通过 X 射线衍射和核磁共振光谱分析了它们的构象：鉴定了 7-氮和酰胺 α-氢原子之间不寻常的分子内相互作用。这些相互作用的强度与酰胺α-取代基的吸电子特性相关。实验和计算方法的结合揭示了当取代基（H、OMe、F、CN）在 7-氮杂吲哚啉支架的 4 位变化时显着的取代基效应。由于这些分子内相互作用也发生在非氟化 N1-酰化 7-氮杂二氢吲哚和类似的杂环中，因此本研究与药物化学相关：
• Pyrrolopyridines useful as inhibitors of protein kinase
  申请人：Ledeboer Mark

  公开号：US20070135466A1

  公开（公告）日：2007-06-14

  The present invention relates to compounds useful as inhibitors of protein kinases, particularly of JAK family and ROCK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及一种作为蛋白激酶抑制剂的化合物，特别是JAK家族和ROCK家族激酶的抑制剂。本发明还提供了包含所述化合物的药学上可接受的组合物，并提供了使用该组合物治疗各种疾病、病况或疾患的方法。
• 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators
  作者：Eugene L. Piatnitski Chekler、Rayomond Unwalla、Taukeer A. Khan、Raghuram S. Tangirala、Mark Johnson、Michael St. Andre、James T. Anderson、Thomas Kenney、Sue Chiparri、Chris McNally、Edward Kilbourne、Catherine Thompson、Sunil Nagpal、Gregory Weber、Scott Schelling、Jane Owens、Carl A. Morris、Dennis Powell、Patrick R. Verhoest、Adam M. Gilbert

  DOI：10.1021/jm401625b

  日期：2014.3.27

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.
• Azaindolines: derisking the indoline structural alert
  作者：Eugene L. Piatnitski Chekler、Taukeer A. Khan、Rajanikanth Mamidala、James T. Anderson、Raghuram S. Tangirala、Patrick R. Verhoest、Adam M. Gilbert

  DOI：10.1016/j.tetlet.2011.11.070

  日期：2012.1

  4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrite 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined. (C) 2011 Elsevier Ltd. All rights reserved.