5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-(4-morpholinylcarbonyl)methyl ester | 877270-31-0

• 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: 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-(4-morpholinylcarbonyl)methyl ester
• 英文别名: methyl 13-cyclohexyl-6-(morpholinylcarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate；methyl 13-cyclohexyl-6-(morpholinylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylate；methyl 13-cyclohexyl-6-(morpholine-4-carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate
• CAS: 877270-31-0
• 化学式: C₃₀H₃₂N₂O₄
• 分子量: 484.595
• InChiKey: TUSMAOKVWZYGPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-(4-morpholinylcarbonyl)methyl ester 在 4-二甲氨基吡啶 、 草酰氯 、 sodium hydride 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.67h， 生成 (1aS,12bR)-8-cyclohexyl-N-(dimethylsulfamoyl)-1a-(morpholin-4-ylcarbonyl)-1,1a,2,12b-tetrahydrocyclopropa[d]-indolo[2,1-a][2]benzazepine-5-carboxamide
  参考文献：
  名称：

  Discovery and Preclinical Characterization of the Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  Described herein are structure-activity relationship studies that resulted in the optimization of the activity of members of a class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors. Subsequent iterations of analogue design and syntheses successfully addressed off-target activities, most notably human pregnane X receptor (hPXR) transactivation, and led to significant improvements in the physicochemical properties of lead compounds. Those analogues exhibiting improved solubility and membrane permeability were shown to have notably enhanced pharmacokinetic profiles. Additionally, a series of alkyl bridged piperazine carboxamides was identified as being of particular interest, and from which the compound BMS-791325 (2) was found to have distinguishing antiviral, safety, and pharmacokinetic properties that resulted in its selection for clinical evaluation.

  DOI：

  10.1021/jm4016894
• 作为产物：
  描述：

  methyl 3-cyclohexyl-2-(2-formylphenyl)-1H-indole-6-carboxylate 在 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.33h， 生成 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-(4-morpholinylcarbonyl)methyl ester
  参考文献：
  名称：

  Discovery and Preclinical Characterization of the Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  Described herein are structure-activity relationship studies that resulted in the optimization of the activity of members of a class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors. Subsequent iterations of analogue design and syntheses successfully addressed off-target activities, most notably human pregnane X receptor (hPXR) transactivation, and led to significant improvements in the physicochemical properties of lead compounds. Those analogues exhibiting improved solubility and membrane permeability were shown to have notably enhanced pharmacokinetic profiles. Additionally, a series of alkyl bridged piperazine carboxamides was identified as being of particular interest, and from which the compound BMS-791325 (2) was found to have distinguishing antiviral, safety, and pharmacokinetic properties that resulted in its selection for clinical evaluation.

  DOI：

  10.1021/jm4016894

文献信息

• Indolobenzazepine HCV NS5B inhibitors
  申请人：Bergstrom P. Carl

  公开号：US20070078122A1

  公开（公告）日：2007-04-05

  The invention encompasses compounds and salts of Formulas I, II, III, and IV as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

  这项发明涵盖了Formula I、II、III和IV的化合物和盐，以及使用这些化合物的组合物和方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的患者。
• Inhibitors of HCV replication
  申请人：Hudyma W. Thomas

  公开号：US20060046983A1

  公开（公告）日：2006-03-02

  Indole compounds of Formula I are described. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV. Different forms and compositions comprising the compounds are also described as well as methods of preparing the compounds.

  化合物I的吲哚类化合物已被描述。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的人。还描述了包含这些化合物的不同形式和组成，以及制备这些化合物的方法。
• Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors
  申请人：Meanwell A. Nicholas

  公开号：US20070060565A1

  公开（公告）日：2007-03-15

  The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

  该发明涵盖了Formula I的化合物，其药用盐，组合物以及使用这些化合物的方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的患者。
• Compounds for the Treatment of Hepatitis C
  申请人：Yeung Kap-Sun

  公开号：US20080226592A1

  公开（公告）日：2008-09-18

  The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

  该发明涵盖了式I的化合物，其药用盐，组合物以及使用这些化合物的方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的患者。
• Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
  申请人：Meanwell A. Nicholas

  公开号：US20070184024A1

  公开（公告）日：2007-08-09

  The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

  该发明涵盖了I式化合物，其药学上可接受的盐，组合物以及使用该化合物的方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的患者。