1-acetyl-1,2,3,5-tetrahydropyrrolo<2,3-f>indole | 40995-78-6

• 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: 1-acetyl-1,2,3,5-tetrahydropyrrolo<2,3-f>indole
• 英文别名: 1-acetyl-1,2,3,5-tetrahydro-pyrrolo[2,3-f]indole；1-acetyl-2,3-dihydropyrrolo[2,3-f]indole；1-Acetyl-1,2,3,5-tetrahydropyrrolo[2,3-f]indole；1-(6,7-dihydro-1H-pyrrolo[2,3-f]indol-5-yl)ethanone
• CAS: 40995-78-6
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: UZQLEMVKVAREMX-UHFFFAOYSA-N

物化性质

• 沸点：
  495.0±33.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-acetyl-1,2,3,5-tetrahydropyrrolo<2,3-f>indole 在 sodium hydroxide 、 sodium hydride 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 8.0h， 生成 5-甲基-1-(3-吡啶羰基)-1,2,3,5-四氢吡咯并[2,3-f]吲哚
  参考文献：
  名称：

  5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: A Novel 5-HT2C/5-HT2B Receptor Antagonist with Improved Affinity, Selectivity, and Oral Activity

  摘要：

  The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pK(I) 8.0) and 5-HT2B receptors (pA(2) 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pK(I) <6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pK(B) 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

  DOI：

  10.1021/jm00014a004
• 作为产物：
  描述：

  1-acetyl-5-(trifluoroacetyl)-1,2,3,5-tetrahydropyrrolo<2,3-f>indole 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以80%的产率得到1-acetyl-1,2,3,5-tetrahydropyrrolo<2,3-f>indole
  参考文献：
  名称：

  5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: A Novel 5-HT2C/5-HT2B Receptor Antagonist with Improved Affinity, Selectivity, and Oral Activity

  摘要：

  The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pK(I) 8.0) and 5-HT2B receptors (pA(2) 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pK(I) <6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pK(B) 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

  DOI：

  10.1021/jm00014a004

文献信息

• Method for synthesis of aryl difluoromethyl ethers
  申请人：SmithKline Beecham Corporation

  公开号：US05731477A1

  公开（公告）日：1998-03-24

  This invention relates to a method for preparing difluoromethyl ethers, thiols and amines without using chlorofluorocarbon gases. The intermediates prepared by this method can be used to make certain compounds which act as PDE IV inhibitors which are useful for treating asthma and other diseases implicated with the PDE IV isozyme.

  这项发明涉及一种制备二氟甲基醚、硫醇和胺的方法，而不使用氯氟烃气体。通过这种方法制备的中间体可用于制备某些化合物，这些化合物作为PDE IV抑制剂，对治疗哮喘和其他与PDE IV同工酶有关的疾病有用。
• Bicyclic compounds as ligands for 5-HT1 receptors
  申请人：SmithKline Beecham plc

  公开号：US06391891B1

  公开（公告）日：2002-05-21

  The invention relates to compounds which are ligands for 5HT1, of formula (I) Wherein L, Q, Ra, Rb and Ry are as defined in the specification, processes for their preparation and their pharmaceutical composition as well as their use in the treatment of anxiety and depression.

  该发明涉及一种5HT1配体化合物，其化学式为(I)，其中L、Q、Ra、Rb和Ry如规范中所定义，以及它们的制备过程、药物组合物以及它们在焦虑和抑郁症治疗中的应用。
• Synthesis, Biological Activity, and Molecular Modeling Studies of Selective 5-HT_2C/2B Receptor Antagonists
  作者：Ian T. Forbes、Steven Dabbs、D. Malcolm Duckworth、Peter Ham、Graham E. Jones、Frank D. King、Damian V. Saunders、Frank E. Blaney、Christopher B. Naylor、Gordon S. Baxter、Thomas P. Blackburn、Guy A. Kennett、Martyn D. Wood

  DOI：10.1021/jm960571v

  日期：1996.1.1

  The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT2C receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor. In a complementary approach, docking of 2 into our model of the 5-HT2C receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT2C receptor for leucine residues in the 5-HT2A receptor is believed to account for the observed 5-HT2C/5-HT2A selectivity with 2.
• CONDENSED INDOLE DERIVATIVES AS 5HT 2C? AND 5HT 2B? ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0656003A1

  公开（公告）日：1995-06-07
• METHOD FOR SYNTHESIS OF ARYL DIFLUOROMETHYL ETHERS AND THE LIKE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0812308B1

  公开（公告）日：2005-03-16