(S-)(-)-4,5-Dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine | 142149-81-3

• 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: (S-)(-)-4,5-Dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine
• 英文别名: (RS)-4,5-dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine；4,5-dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine；3-Ethyl-2-methyl-5-phenyl-1,5-dihydro-2,4-benzodiazepine
• CAS: 142149-81-3
• 化学式: C₁₈H₂₀N₂
• 分子量: 264.37
• InChiKey: WXIRADDCDHBYHR-UHFFFAOYSA-N

物化性质

• 沸点：
  424.4±45.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  15.6
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S-)(-)-4,5-Dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine 在 钯 ammonium formate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-Methyl-N-[[2-(phenylmethyl)phenyl]methyl]propanimidamide
  参考文献：
  名称：

  Antiarrhythmic diarylamidines

  摘要：

  新型二芳基胺基吡唑衍生物，以及利用公式I、II、III和IV中的新型和相关已知的二芳基胺基吡唑衍生物治疗哺乳动物心律失常的组合物和方法。

  公开号：

  US05286752A1
• 作为产物：
  描述：

  N-methyl-α'-phenyl-1,2-phenylenedimethanamine dihydrochloride 、 原丙酸三乙酯 在 sodium acetate 、 溶剂黄146 作用下， 反应 24.0h， 生成 (S-)(-)-4,5-Dihydro-3-ethyl-4-methyl-1-phenyl-1H-2,4-benzodiazepine
  参考文献：
  名称：

  4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: Novel antiarrhythmic agents

  摘要：

  A series of 4,5-dihydro-1-phenyl-1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact with sodium and potassium channels and prolong the ventricular effective refractory period (ERP) in anesthetized guinea pigs. Concomitant displacement of radiolabeled bactrachotoxin from site II in Na+ channels and of radiolabeled dofetilide from delayed rectifier K+ channels was evident with all members of this chemical series at a concentration of 10 muM. Structure-activity relationship (SAR) studies using a paced guinea pig model to assess prolongation of the ERP indicated that methyl or ethyl at the 1-position had little effect on activity, while larger groups caused a diminution of activity. Compounds with substituents at either the 3- or 4-position that increased lipophilicity generally were more potent; however, too many lipophilic substituents simultaneously at positions 1, 3, and 4 resulted in less active compounds. Substituents on either aromatic ring had little influence on activity, and phenyl at the 5-position resulted in a significant reduction in antiarrhythmic activity. When two sets of enantiomerically pure compounds were tested in the guinea pig, chirality was shown to be important for activity of 8, where the (R)-enantiomer was the more active, but not in the case of 15, where the enantiomers were equiactive. Several compounds in this series increased the threshold for vertricular fibrillation and refractoriness in myocardially-infarcted anesthetized cata and delayed the onset of aconitine-induced arrhythmias in anesthetized guinea pigs following intravenous dosing. Moreover, these compounds possessed oral antiarrhythmic activity in conscious myocardially-infarcted dogs. Compound R-15 has been advanced for further biological and toxicological evaluations.

  DOI：

  10.1021/jm00074a017

文献信息

• Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents
  申请人：SANOFI

  公开号：EP0475527B1

  公开（公告）日：1998-02-25
• US5286752A
  申请人：——

  公开号：US5286752A

  公开（公告）日：1994-02-15
• 4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: Novel antiarrhythmic agents
  作者：Robert E. Johnson、Eugene R. Baizman、Carolyn Becker、Eric A. Bohnet、Rebecca H. Bell、Nancy C. Birsner、Carl A. Busacca、Philip M. Carabateas、Christopher C. Chadwick

  DOI：10.1021/jm00074a017

  日期：1993.10

  A series of 4,5-dihydro-1-phenyl-1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact with sodium and potassium channels and prolong the ventricular effective refractory period (ERP) in anesthetized guinea pigs. Concomitant displacement of radiolabeled bactrachotoxin from site II in Na+ channels and of radiolabeled dofetilide from delayed rectifier K+ channels was evident with all members of this chemical series at a concentration of 10 muM. Structure-activity relationship (SAR) studies using a paced guinea pig model to assess prolongation of the ERP indicated that methyl or ethyl at the 1-position had little effect on activity, while larger groups caused a diminution of activity. Compounds with substituents at either the 3- or 4-position that increased lipophilicity generally were more potent; however, too many lipophilic substituents simultaneously at positions 1, 3, and 4 resulted in less active compounds. Substituents on either aromatic ring had little influence on activity, and phenyl at the 5-position resulted in a significant reduction in antiarrhythmic activity. When two sets of enantiomerically pure compounds were tested in the guinea pig, chirality was shown to be important for activity of 8, where the (R)-enantiomer was the more active, but not in the case of 15, where the enantiomers were equiactive. Several compounds in this series increased the threshold for vertricular fibrillation and refractoriness in myocardially-infarcted anesthetized cata and delayed the onset of aconitine-induced arrhythmias in anesthetized guinea pigs following intravenous dosing. Moreover, these compounds possessed oral antiarrhythmic activity in conscious myocardially-infarcted dogs. Compound R-15 has been advanced for further biological and toxicological evaluations.
• Antiarrhythmic diarylamidines
  申请人：Sterling Winthrop Inc.

  公开号：US05286752A1

  公开（公告）日：1994-02-15

  Novel diarylamidines, and compositions and methods for treating cardiac arrhythmias in mammals utilizing the novel and related known diarylamidines of formula I, II, III and IV ##STR1##

  新型二芳基胺基吡唑衍生物，以及利用公式I、II、III和IV中的新型和相关已知的二芳基胺基吡唑衍生物治疗哺乳动物心律失常的组合物和方法。