(1aR,12bS)-8-cyclohexyl-N-(dimethylsulfamoyl)-11-methoxy-1a-(((2R)-2-(methoxymethyl)morpholin-4-yl)carbonyl)-1,1a,2,12b-tetrahydrocyclopropa[d]indolo[2,1-a][2]-benzazepine-5-carboxamide | 1532561-34-4

• 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: (1aR,12bS)-8-cyclohexyl-N-(dimethylsulfamoyl)-11-methoxy-1a-(((2R)-2-(methoxymethyl)morpholin-4-yl)carbonyl)-1,1a,2,12b-tetrahydrocyclopropa[d]indolo[2,1-a][2]-benzazepine-5-carboxamide
• 英文别名: (8S,10R)-19-cyclohexyl-N-(dimethylsulfamoyl)-5-methoxy-10-[(2R)-2-(methoxymethyl)morpholine-4-carbonyl]-12-azapentacyclo[10.7.0.02,7.08,10.013,18]nonadeca-1(19),2(7),3,5,13(18),14,16-heptaene-15-carboxamide
• CAS: 1532561-34-4
• 化学式: C₃₅H₄₄N₄O₇S
• 分子量: 664.823
• InChiKey: RFOPMFZIQCADIJ-RSWONJOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  47
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-溴-3-环己基-1H-吲哚-6-羧酸甲酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N'-羰基二咪唑 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 54.08h， 生成 (1aR,12bS)-8-cyclohexyl-N-(dimethylsulfamoyl)-11-methoxy-1a-(((2R)-2-(methoxymethyl)morpholin-4-yl)carbonyl)-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