1-(2,4-difluorophenyl)-4,5-dihydro-3,4-dimethyl-1H-2,4-benzodiazepine | 158422-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1-(2,4-difluorophenyl)-4,5-dihydro-3,4-dimethyl-1H-2,4-benzodiazepine
• 英文别名: (+)-4,5-dihydro-3,4-dimethyl-1-(2,4-difluorophenyl)-1H-2,4-benzodiazepine；5-(2,4-Difluorophenyl)-2,3-dimethyl-1,5-dihydro-2,4-benzodiazepine
• CAS: 158422-72-1
• 化学式: C₁₇H₁₆F₂N₂
• 分子量: 286.324
• InChiKey: LCXCUYYOJCAYKH-UHFFFAOYSA-N

物化性质

• 沸点：
  389.0±42.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  15.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,4-difluorophenyl)-4,5-dihydro-3,4-dimethyl-1H-2,4-benzodiazepine 在 乙二胺 作用下， 以 甲苯 为溶剂， 反应 24.0h， 生成 (S)-N-methyl-α'-(2,4-difluorophenyl)benzenedimethanamine
  参考文献：
  名称：

  4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: A Novel Class III Antiarrhythmic Agents

  摘要：

  A series of 4,5-dihydro-3-[2-(methanesulfonamidophenyl)ethyl]-1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact at the delayed rectifier myocardial potassium channels (I-Kr) and prolong the ventricular effective refractory period (ERP) in rabbit isolated Langendorff heart preparations. Structure-activity relationship (SAR) studies based upon prolongation of ERP indicate that placement of the sulfonamido group is important for potent activity in this model. Furthermore, methanesulfonamido has enhanced activity over its ethyl or trifluoromethyl analogs. Slightly greater activity was observed in compounds that had a heteroatom in the ethyl bridge that connects the methanesulfonamidophenyl to the benzodiazepine. Further incremental improvements in activity were noted when the 1-phenyl ring was substituted with a variety of substituents. Chirality of the compounds of interest in this series does not appear to influence activity in this model. Several of these compounds were chosen for advanced evaluation, and all possess high selectivity for blockade of potassium current in hearts relative to other ion channels. In addition, these compounds prolong cardiac refractoriness in dogs following oral dosing. Thus, these agents may represent potential new class III agents, but with the potential liability of myocardial I-Kr blockers.

  DOI：

  10.1021/jm00014a008
• 作为产物：
  描述：

  原乙酸三甲酯 、 N-methyl-α'-(2,4-difluorophenyl)benzenedimethanamine dihydrochloride 在 sodium acetate 作用下， 以 甲醇 为溶剂， 以72%的产率得到1-(2,4-difluorophenyl)-4,5-dihydro-3,4-dimethyl-1H-2,4-benzodiazepine
  参考文献：
  名称：

  4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: A Novel Class III Antiarrhythmic Agents

  摘要：

  A series of 4,5-dihydro-3-[2-(methanesulfonamidophenyl)ethyl]-1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact at the delayed rectifier myocardial potassium channels (I-Kr) and prolong the ventricular effective refractory period (ERP) in rabbit isolated Langendorff heart preparations. Structure-activity relationship (SAR) studies based upon prolongation of ERP indicate that placement of the sulfonamido group is important for potent activity in this model. Furthermore, methanesulfonamido has enhanced activity over its ethyl or trifluoromethyl analogs. Slightly greater activity was observed in compounds that had a heteroatom in the ethyl bridge that connects the methanesulfonamidophenyl to the benzodiazepine. Further incremental improvements in activity were noted when the 1-phenyl ring was substituted with a variety of substituents. Chirality of the compounds of interest in this series does not appear to influence activity in this model. Several of these compounds were chosen for advanced evaluation, and all possess high selectivity for blockade of potassium current in hearts relative to other ion channels. In addition, these compounds prolong cardiac refractoriness in dogs following oral dosing. Thus, these agents may represent potential new class III agents, but with the potential liability of myocardial I-Kr blockers.

  DOI：

  10.1021/jm00014a008

文献信息

• Aryl-fused and hetaryl-fused-2,4-diazocine antiarrhythmic agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0597540A1

  公开（公告）日：1994-05-18

  Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, wherein    A is an aryl, cycloalkyl or hetaryl or substituted aryl ring    R¹ is hydrogen, alkyl, aralkyl, aryl, hetaryl or substituted aryl;    R² is hydrogen, alkyl, aralkyl, aryl or substituted alkyl or aryl;    R³ is alkyl, aryl, aralkyl, hetaryl or heteroatom substituted alkyl, aryl, aralkyl or hetaryl;    R⁴ is hydrogen, alkyl or substituted alkyl;    R⁵ is hydrogen, alkyl, aryl, aralkyl, hetaryl or substituted aryl, pharmaceutical compositions containing these and methods of treating cardiac arrhythmia with the compounds of formula XXXVI are disclosed.

  式 XXXVI 的芳基融合-2,4-二氮杂卓和正十八烷基融合-2,4-二氮杂卓、 其中 A 是芳基环、环烷基环、正十八烷基环或取代的芳基环 R¹ 是氢、烷基、芳烷基、芳基、正烷基或取代的芳基； R² 是氢、烷基、芳烷基、芳基或取代的烷基或芳基； R³ 是烷基、芳基、芳烷基、正烷基或杂原子取代的烷基、芳基、芳烷基或正烷基； R⁴ 是氢、烷基或取代的烷基； R⁵ 是氢、烷基、芳基、芳烷基、庚基或取代的芳基、 本发明公开了含有这些化合物的药物组合物以及用式 XXXVI 化合物治疗心律失常的方法。
• US5380721A
  申请人：——

  公开号：US5380721A

  公开（公告）日：1995-01-10
• US5624922A
  申请人：——

  公开号：US5624922A

  公开（公告）日：1997-04-29