双(1H-吲哚-2-基)甲酮 | 200706-56-5

• 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
• 中文名称: 双(1H-吲哚-2-基)甲酮
• 英文名称: bisindol-2-ylmethan-1-one
• 英文别名: bis(1H-2-indolyl)methanone；bis(1H-2-indolyl) ketone；indolyl ketone；di-indol-2-yl ketone；Di-indol-2-yl-keton；di(1H-indol-2-yl)methanone；bis(1H-indol-2-yl)methanone
• CAS: 200706-56-5
• 化学式: C₁₇H₁₂N₂O
• 分子量: 260.295
• InChiKey: GQJIQKLWZMQQGO-UHFFFAOYSA-N

物化性质

• 熔点：
  198 °C
• 沸点：
  546.7±25.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.6
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  双(1H-吲哚-2-基)甲酮 在 氢氧化钾 、 乙基溴化镁 、 sodium hydride 、 一水合肼 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 二乙二醇 为溶剂， 反应 6.5h， 生成 2-benzyloxymethyl-8-(2-(N,N-dimethylamino)ethyl)-1,2,3,8,9,10-hexahydroindolo[3',2':5,6]pyrrolo[3',4':3,4]cyclohepta[b]indole-1,3-dione
  参考文献：
  名称：

  同型心黄素：环扩Arcyriaflavin类似物的合成。

  摘要：

  通过形成2,2'-桥联的双吲哚与3,4-二溴-2,5-二氢-1H-2,5-吡咯二酮的反应可以有效地完成形成arcyriaflavin同系物的扩环咔唑系统的构建。格氏条件下的衍生品。中心环中最多可以有9个成员。也可以在吲哚体系或酰亚胺-N处取代。通过核磁共振，X射线和半经验量子化学计算方法研究了均硬环黄素作为刚性硬环黄素与柔性硬环红素之间的交联结构。

  DOI：

  10.1021/jo981926g
• 作为产物：
  描述：

  1-苯基磺酰-1H-吲哚-2-羰酰氯 在 正丁基锂 、 四丁基氟化铵 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 双(1H-吲哚-2-基)甲酮
  参考文献：
  名称：

  Bis(1H-2-indolyl)methanones as a Novel Class of Inhibitors of the Platelet-Derived Growth Factor Receptor Kinase

  摘要：

  The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone group as well as substitution at both indoles result in weak or no activity. An ATP binding site model, derived by homology from the FGFR-1 tyrosine kinase crystal structure suggesting hydrogen bonds of one indole NH and the methanone oxygen with the backbone carbonyl and amide, respectively, of Cys684, explains why only one indole moiety is open for substitution and locates groups in the 5- or 6-position outside the pocket. The hitherto most active derivatives, 39, 53 and 67, inhibit both isoforms of the PDGF receptor kinase in intact cells, with IC50 of 0.1-0.3 muM, and purified PDGFbeta-receptor in vitro, with IC50 of 0.09, 0.1, or 0.02 muM, respectively. PDGF-stimulated DNA synthesis is inhibited by these derivatives with IC50 values of 1-3 muM. Kinetic analysis of 53 showed an ATP-competitive mode of inhibition. The compounds are inactive or weakly active toward a number of other tyrosine kinases, including the FGF receptor 1, EGF receptor, and c-Src kinase, as well as toward serine-threonine kinases, including different PKC isoforms and GRK2, and appear therefore selective for PDGF receptor inhibition.

  DOI：

  10.1021/jm010988n

文献信息

• [EN] SYNTHESIS, PHARMACOLOGY AND USE OF NEW AND SELECTIVE FMS-LIKE TYROSINE KINASE 3 (FLT3) FLT3 INHIBITORS<br/>[FR] SYNTHÈSE, PHARMACOLOGIE ET UTILISATION DE NOUVEAUX INHIBITEURS SÉLECTIFS DE LA TYROSINE KINASE 3 DE TYPE FMS FLT3 (FLT3)
  申请人：UNIV REGENSBURG

  公开号：WO2019034538A1

  公开（公告）日：2019-02-21

  The present invention relates to small molecule compounds of formula (I) and their use as FLT3 inhibitors for the treatment of various diseases, such as acute myeloid leukemia (AML). The present invention further relates to methods of synthesizing the compounds and methods of treatment.

  本发明涉及式(I)的小分子化合物及其作为FLT3抑制剂用于治疗各种疾病，如急性髓系白血病（AML）。本发明还涉及合成这些化合物的方法和治疗方法。
• [EN] MAP4K4 (HGK) Inhibitors<br/>[FR] INHIBITEURS DE MAP4K4 (HGK)
  申请人：STANFORD RES INST INT

  公开号：WO2016114816A1

  公开（公告）日：2016-07-21

  The invention provides mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibitors, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant diminution of tumor cell growth, cancer or metastasis.

  该发明提供了有丝分裂原激活蛋白激酶激酶激酶激酶4（MAP4K4）抑制剂，以及其药用盐、氢化物和立体异构体。这些化合物被用于制备药物组合物，并用于制备方法，包括使用有效量的该化合物或组合物治疗需要的人，以及检测结果肿瘤细胞生长、癌症或转移的减少。
• Iodine-mediated intramolecular amination of ketones: the synthesis of 2-acylindoles and 2-acylindolines by tuning N-protecting groups
  作者：Wen-Chao Gao、Shan Jiang、Ruo-Lin Wang、Chi Zhang

  DOI：10.1039/c3cc40797g

  日期：——

  A general method for constructing both 2-acylindoles and 2-acylindolines via I2-mediated intramolecular C-N bond formation is presented, and the selective formation of either 2-acylindoles or 2-acylindolines just depends on the nitrogen protecting groups used in the same substrate skeletons.

  提出了通过I2介导的分子内CN键形成构建2-acylindoles和2-acylindolines的一般方法，并且2-acylindoles或2-acylindolines的选择性形成仅取决于在相同底物骨架中使用的氮保护基团。 。
• Cyclopentyl indole derivatives
  申请人：——

  公开号：US20040077705A1

  公开（公告）日：2004-04-22

  The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts or solvates thereof and pharmaceutically acceptable formulations comprising said compounds 1 useful for the treatment of premature ejaculation, depression, attention deficit hyperactivity disorder, obsessive-compulsive disorder, post-traumatic stress disorder and substance abuse disorders.

  本发明涉及公式（I）的化合物及其药学上可接受的盐或溶剂，以及包含所述化合物的药学上可接受的制剂，用于治疗早泄、抑郁症、注意力缺陷多动障碍、强迫症、创伤后应激障碍和物质滥用障碍。
• Indole derivatives and their use for the treatment of malignant and other diseases based on pathological proliferation
  申请人：——

  公开号：US20030008898A1

  公开（公告）日：2003-01-09

  The invention relates to tyrosine kinase inhibitors of the bis-indolyl compound type of the general formula I: 1 pharmaceuticals containing them and their use for the treatment of malignant and other diseases based on pathological cell proliferation.

  本发明涉及一种通式I的双吲哚基酪氨酸激酶抑制剂，以及含有它们的药物，以及它们用于治疗基于病理细胞增殖的恶性和其他疾病的用途。