3-amino-1H-indole-2-carbonitrile | 1192690-93-9

• 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: 3-amino-1H-indole-2-carbonitrile
• 英文别名: 3-aminoindole-2-carbonitrile
• CAS: 1192690-93-9
• 化学式: C₉H₇N₃
• 分子量: 157.175
• InChiKey: GHLTXKHMFVGIDQ-UHFFFAOYSA-N

物化性质

• 沸点：
  441.2±30.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-amino-1H-indole-2-carbonitrile 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 5H-pyrimido[5,4-b]indol-4-amine
  参考文献：
  名称：

  Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives

  摘要：

  我们先前强调了6,5,6-融合三环类4-氨基喹唑啉作为激酶抑制剂在微摩尔到纳摩尔范围内的IC50值的兴趣。为了生成化学库，使用甲酰胺介导的氰基胺前体的环化反应在微波辐射下进行，采用环保的方法。为了更深入地探索这种三环骨架的药理学兴趣，中心的五元环，即噻吩或呋喃，被替换为吡咯，以制备受到harmine启发的9H-嘧啶并[5,4-b]-和[4,5-b]吲哚-4-胺衍生物。最终产品的抑制效力被测定对四种蛋白激酶（CDK5/p25、CK1δ/ε、GSK3α/β和DYRK1A）。结果，我们已经确定了有前途的化合物，靶向CK1δ/ε和DYRK1A，显示微摩尔和亚微摩尔的IC50值。

  DOI：

  10.3390/ph13050089
• 作为产物：
  描述：

  N-(2-cyanophenyl)-N-(cyanomethyl)amine 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 120.0 ℃ 、1.24 MPa 条件下， 反应 0.13h， 以78%的产率得到3-amino-1H-indole-2-carbonitrile
  参考文献：
  名称：

  Microwave assisted synthesis of 3-aminoindole-2-carbonitriles from anthranilonitriles via N-unprotected 2-(cyanomethylamino)benzonitriles

  摘要：

  Anthranilonitrile 3a, 4,5-dimethoxyanthranilonitrile 3b and 5-nitroanthranilonitrile 3c, react with paraformaldehyde, KCN and ZnCl2 in acetic acid under acid catalysis (H2SO4) in a sealed tube at ca. 55 degrees C to give the corresponding 2-(cyanomethylamino)benzonitriles 4a-c in 96, 86 and 57% yields, respectively. Thorpe-Ziegler cyclisation of the N-unprotected 2-(cyanomethylamino)benzonitriles 4a-c with K2CO3 in EtOH at elevated temperatures and pressures using either microwave heating or conventional heating in a sealed tube gives 3-amino, 3-amino-5,6-dimethoxy, and 3-amino-5-nitro-indole-2-carbonitriles 2a-c in moderate to good yields. All new compounds are fully characterised. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.11.067

文献信息

• The conversion of 2-(4-chloro-5H-1,2,3-dithiazolylideneamino)benzonitriles into 3-aminoindole-2-carbonitriles using triphenylphosphine
  作者：Sophia S. Michaelidou、Panayiotis A. Koutentis

  DOI：10.1016/j.tet.2009.07.064

  日期：2009.10

  2-(4-Chloro-5H-1,2,3-dithiazolylideneamino)benzonitrile 1a reacts with triphenylphosphine (4 equiv) in the presence of water (2 equiv) to afford anthranilonitrile 2a, 3-aminoindole-2-carbonitrile 3a and (2-cyanoindol-3-yl)iminotriphenylphosphorane 4a, together with triphenylphosphine sulfide and oxide. The use of polymer bound triphenylphosphine provides cleaner reaction mixtures. 2-(4-Chloro-5H-1

  2-（4-氯-5 H -1,2,3-二噻唑基亚氨基氨基）苄腈1a在水（2当量）存在下与三苯基膦（4当量）反应生成蒽腈2a，3-氨基吲哚-2-腈3a和（2-氰基吲哚-3-基）亚氨基三苯基膦4a以及三苯基膦硫化物和氧化物。聚合物键合的三苯膦的使用提供了更清洁的反应混合物。2-（4-氯-5 H -1,2,3-二噻唑基亚氨基）-4,5-二甲氧基苄腈1h经三苯膦处理后不生成相应的吲哚，但生成6,7-二甲氧基喹唑啉-2-腈5（15％ ）和2-氰基-4,5-二甲氧基氰基硫代甲酰苯胺6（36％）。总共准备并完全表征了七个新的3-氨基吲哚-2-腈3a – g。
• The conversion of 2-cyano cyanothioformanilides into 3-aminoindole-2-carbonitriles using triphenylphosphine
  作者：Panayiotis A. Koutentis、Sophia S. Michaelidou

  DOI：10.1016/j.tet.2010.06.020

  日期：2010.8

  react with triphenylphosphine and p-toluenesulfonic acid in MeOH to give 3-aminoindole-2-carbonitriles 2b–f in 63–75% yields. Under analogous conditions 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide 2g gives only 4,5-dimethoxyanthranilonitrile 8g and 4,6,7-trimethoxyquinazoline-2-carbonitrile 14g, but in refluxing dry PhMe in the absence of p-toluenesulfonic acid 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide

  2-氰基cyanothioformanilide 3A与在水的存在下发生反应的三苯基膦，得到2-（氰基亚甲基氨基）苄腈4a中，2-（cyanomethylamino）苄腈5，3-氨基吲哚-2-甲腈2A和（2-氰基吲哚-3-基）iminotriphenylphosphorane 6a。在对甲苯磺酸在MeOH中的存在下，2-氰基氰基硫代甲酰甲酰胺3a与三苯基膦（2当量）之间的反应以90％的产率得到3-氨基吲哚-2-腈2a。在相同条件下，2-（氰基亚甲基氨基）苄腈4a得到蒽腈8a，3-氨基吲哚-2-腈2a和N-（2-氰基苯基）甲酰胺9。此外，取代的2-氰基氰基硫代甲酰胺基化物3b - f与三苯基膦和对甲苯磺酸在MeOH中反应，以63-75％的收率得到3-氨基吲哚-2-腈2b - f。在类似条件下，2-氰基-4,5-二甲氧基苯基氰基硫代甲酰苯胺2g仅产生4,5-二甲氧基蒽腈8g和4,6,7-三甲氧
• Pro-Neurogenic Compounds
  申请人：Board of Regents of The University of Texas System

  公开号：US20140057900A1

  公开（公告）日：2014-02-27

  Compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.

  本发明公开了刺激神经发生（例如，产后神经发生，包括产后海马和下丘脑神经发生）和/或保护神经细胞免于细胞死亡的化合物和方法。体内活性测试表明，这些化合物可能在精神神经疾病和/或神经退行性疾病中具有治疗益处，例如精神分裂症、重度抑郁症、双相情感障碍、正常衰老、癫痫、创伤性脑损伤、创伤后应激障碍、帕金森病、阿尔茨海默病、唐氏综合症、脊髓小脑共济失调、肌萎缩侧索硬化症、亨廷顿病、中风、放射治疗、慢性压力、滥用神经活性药物、视网膜退化、脊髓损伤、周围神经损伤、与各种情况相关的生理体重减轻，以及与正常衰老、化疗等相关的认知衰退。
• [EN] PYRIDO [3',2' :4,5] THIENO [3, 2-D] PYRIMIDIN- 4 - YLAMINE DERIVATIVES AND THEIR THERAPEUTICAL USE<br/>[FR] DÉRIVÉS DE PYRIDO[3',2':4,5]THIÉNO[3,2-D]PYRIMIDIN-4-YLAMINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：BAELL JONATHAN BAYLDON

  公开号：WO2012131297A1

  公开（公告）日：2012-10-04

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain fused triaryl amine compounds of the following formula (for convenience, collectively referred to herein as "FTA compounds"), which, inter alia, inhibit LIM kinase (LIMK) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit LIMK activity, and in the treatment of diseases and conditions that are mediated by LIMK, that are ameliorated by the inhibition of LIMK activity, etc., including proliferative conditions such as cancer (e.g., breast cancer, prostate cancer, melanoma, glioma, etc.), as well as vasodilation (including, e.g., hypertension, angina, cerebral vasospasm, and ischemia following subarachnoid hemorrhage), neurodegenerative disorders, atherosclerosis, fibrosis, and inflammatory diseases (including, e.g., Crohn's disease and chronic obstructive pulmonary disease (COPD)), and glaucoma (also known as ocular hypertension).

  本发明一般涉及治疗化合物领域，更具体地涉及以下公式的某些融合三芳基胺化合物（为方便起见，统称为“FTA化合物”），该化合物等等可以抑制LIM激酶（LIMK）活性。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体内和体外抑制LIMK活性，以及治疗由LIMK介导，通过抑制LIMK活性得到改善等疾病和症状的用途，包括增生性疾病，如癌症（如乳腺癌、前列腺癌、黑色素瘤、胶质瘤等），以及血管扩张（包括高血压、心绞痛、脑血管痉挛和蛛网膜下腔出血后缺血等）、神经退行性疾病、动脉硬化、纤维化和炎症性疾病（如克罗恩病和慢性阻塞性肺病（COPD）），以及青光眼（又称眼高压）等。
• Study of N1-alkylation of indoles from the reaction of 2(or 3)-aminoindole-3-(or 2)carbonitriles with DMF-dialkylacetals
  作者：Yvonnick Loidreau、Sigismund Melissen、Vincent Levacher、Cédric Logé、Jérôme Graton、Jean-Yves Le Questel、Thierry Besson

  DOI：10.1039/c2ob25747e

  日期：——

  The condensation of 2-aminoindole-3-carbonitriles and their 3-aminoindole-2-carbonitrile isomers with various DMF-dialkoxyacetals was investigated under microwaves. The appearance of reactive and versatile alkoxyiminium species allowed convenient access to indole precursors of building blocks with potential biological activity. The experimental results have been rationalised using DFT calculations of theoretical descriptors based on the electrostatic potential.

  在微波条件下，研究了 2-氨基吲哚-3-碳腈及其 3-氨基吲哚-2-碳腈异构体与各种 DMF 二烷氧基乙醛的缩合。反应性和多功能烷氧基亚氨基的出现，为获得具有潜在生物活性的吲哚前体构件提供了便利。实验结果通过基于静电位的理论描述符的 DFT 计算得到了合理的解释。