4-(1H-indol-3-yl)-1H-pyrazol-3-ol | 714274-06-3

• 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: 4-(1H-indol-3-yl)-1H-pyrazol-3-ol
• 英文别名: 4-(1H-indol-3-yl)-1,2-dihydropyrazol-3-one
• CAS: 714274-06-3
• 化学式: C₁₁H₉N₃O
• 分子量: 199.212
• InChiKey: CIVJHZNMPMVSCC-UHFFFAOYSA-N

物化性质

• 熔点：
  260 °C (decomp)(Solv: ethyl acetate (141-78-6))
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  丁炔二酸二甲酯 、 4-(1H-indol-3-yl)-1H-pyrazol-3-ol 以 甲醇 为溶剂， 反应 4.0h， 生成 dimethyl 2-[3-hydroxy-4-(1H-indol-3-yl)-1H-pyrazol-1-yl]but-2-ene-1,4-dioate 、 dimethyl 2-[3-hydroxy-4-(1H-indol-3-yl)-1H-pyrazol-1-yl]but-2-ene-1,4-dioate
  参考文献：
  名称：

  Application of alkyl 3-dimethylamino-2-(1H-indol-3-yl)propenoates in the synthesis of 3-heteroarylindoles

  摘要：

  Methyl and ethyl 3-dimethylamino-2-(indol-3-yl)propenoate were prepared from alkyl 3-indoleacetates and tert-butoxy-bis(dimethylamino)methane. Upon treatment of these two N,N-dimethylenaminones with alpha-heteroarylamines as N,N-1,3-dinucleophiles, condensed indolylpyrimidones as meridianine analogues were obtained in poor to moderate yields, while intramolecular condensations with C,O-1.3-dinucleophiles furnished condensed indolylpyranones. Similarly, reaction with hydrazinium chloride led to indolylpyrazolol, while with 3-chloro-6-hydrazinopyridazine only the dimethylamine substitution took place to give the corresponding hydrazone. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.03.075
• 作为产物：
  描述：

  甲基吲哚-3-乙酸盐 在 sodium hydride 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 48.0h， 生成 4-(1H-indol-3-yl)-1H-pyrazol-3-ol
  参考文献：
  名称：

  Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of indolylpyrazolones and indolylpyridazinedione

  摘要：

  The synthesis of 5-indolylpyrazol-3-one, 4-indolylpyrazol-3-one and 4-indolyl-pyridazin-3,6-dione is reported. Their Chkl inhibitory properties have been evaluated and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, human colon carcinoma HT29 and HCT116 have been deter-mined. 4-Indolyl-pyridazin-3,6-dione is inactive against Chk1 and exhibits weak cytotoxicities toward the tumor cell lines tested. The IC50 values toward Chkl of the two indolylpyrazolones are identical and are in the micromolar range, but the cytotoxicities of 4-indolylpyrazol-3-one are significantly stronger than those of 5-indolylpyrazol-3-one. Since 4-indolylpyrazol-3-one and 5-indolyipyrazol-3-one can present several conformers and tautorneric forms, molecular modelling in the ATP binding site of Chk1 has been carried out to investigate which form could induce the best stabilization in the active site of the enzyme. To get an insight into the kinase selectivity of these compounds, their inhibitory activities toward Src kinase here evaluated. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.06.012

文献信息

• NOVEL 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE
  申请人：ITEOS THERAPEUTICS

  公开号：US20160263087A1

  公开（公告）日：2016-09-15

  4-(Indol-3-yl)-pyrazole derivative compounds of Formula I or pharmaceutically acceptable enantiomers, salts or solvates thereof are provided. Further provided is the use of the compounds of Formula I as TDO2 inhibitors. Also provided herein is use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity.

  本文提供了式I的4-(Indol-3-yl)-吡唑衍生物化合物或其药学上可接受的对映体、盐或溶剂的使用。本文还提供了利用式I化合物作为TDO2抑制剂的用途。同时，本文还提供了利用式I化合物用于治疗和/或预防癌症、神经退行性疾病如帕金森氏症、阿尔茨海默病和亨廷顿病、慢性病毒感染如丙型肝炎和人类免疫缺陷病毒感染、抑郁症和肥胖症的用途。
• 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE
  申请人：iTeos Therapeutics

  公开号：EP3066090A1

  公开（公告）日：2016-09-14
• [EN] 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE<br/>[FR] DÉRIVÉS DE 4-(INDOL-3-YL)PYRAZOLE, COMPOSITIONS PHARMACEUTIQUES ET PROCÉDÉS D'UTILISATION
  申请人：ITEOS THERAPEUTICS

  公开号：WO2015067782A1

  公开（公告）日：2015-05-14

  The present invention relates to compound of Formula (I) or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as tryptophan 2,3-dioxygenase (TDO2) inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula (I).
• Application of alkyl 3-dimethylamino-2-(1H-indol-3-yl)propenoates in the synthesis of 3-heteroarylindoles
  作者：Renata Jakše、Jurij Svete、Branko Stanovnik、Amalija Golobič

  DOI：10.1016/j.tet.2004.03.075

  日期：2004.5

  Methyl and ethyl 3-dimethylamino-2-(indol-3-yl)propenoate were prepared from alkyl 3-indoleacetates and tert-butoxy-bis(dimethylamino)methane. Upon treatment of these two N,N-dimethylenaminones with alpha-heteroarylamines as N,N-1,3-dinucleophiles, condensed indolylpyrimidones as meridianine analogues were obtained in poor to moderate yields, while intramolecular condensations with C,O-1.3-dinucleophiles furnished condensed indolylpyranones. Similarly, reaction with hydrazinium chloride led to indolylpyrazolol, while with 3-chloro-6-hydrazinopyridazine only the dimethylamine substitution took place to give the corresponding hydrazone. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of indolylpyrazolones and indolylpyridazinedione
  作者：Elisabeth Conchon、Bettina Aboab、Roy M. Golsteyn、Francisco Cruzalegui、Thomas Edmonds、Stéphane Léonce、Bruno Pfeiffer、Michelle Prudhomme

  DOI：10.1016/j.ejmech.2006.06.012

  日期：2006.12

  The synthesis of 5-indolylpyrazol-3-one, 4-indolylpyrazol-3-one and 4-indolyl-pyridazin-3,6-dione is reported. Their Chkl inhibitory properties have been evaluated and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, human colon carcinoma HT29 and HCT116 have been deter-mined. 4-Indolyl-pyridazin-3,6-dione is inactive against Chk1 and exhibits weak cytotoxicities toward the tumor cell lines tested. The IC50 values toward Chkl of the two indolylpyrazolones are identical and are in the micromolar range, but the cytotoxicities of 4-indolylpyrazol-3-one are significantly stronger than those of 5-indolylpyrazol-3-one. Since 4-indolylpyrazol-3-one and 5-indolyipyrazol-3-one can present several conformers and tautorneric forms, molecular modelling in the ATP binding site of Chk1 has been carried out to investigate which form could induce the best stabilization in the active site of the enzyme. To get an insight into the kinase selectivity of these compounds, their inhibitory activities toward Src kinase here evaluated. (c) 2006 Elsevier Masson SAS. All rights reserved.