1H-2,4-苯并二氮卓,4,5-二氢-3,4-二甲基-1-[4-(甲硫基)苯基]- | 158422-65-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 1H-2,4-苯并二氮卓,4,5-二氢-3,4-二甲基-1-[4-(甲硫基)苯基]-
• 英文名称: (+)-4,5-dihydro-3,4-dimethyl-1-(4-methylthiophenyl)-1H-2,4-benzodiazepine
• 英文别名: 2,3-Dimethyl-5-(4-methylsulfanylphenyl)-1,5-dihydro-2,4-benzodiazepine
• CAS: 158422-65-2；158424-72-7；158424-73-8
• 化学式: C₁₈H₂₀N₂S
• 分子量: 296.436
• InChiKey: JRTSFGXULGGEEA-UHFFFAOYSA-N

物化性质

• 沸点：
  466.7±45.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 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：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1H-2,4-苯并二氮卓,4,5-二氢-3,4-二甲基-1-[4-(甲硫基)苯基]- 生成 (S)-2,3-Dimethyl-5-(4-methylsulfanyl-phenyl)-2,5-dihydro-1H-benzo[e][1,3]diazepine
  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：

  O,O'-dibenzoyl-L-tartaric acid 以 乙醇 为溶剂， 生成 1H-2,4-苯并二氮卓,4,5-二氢-3,4-二甲基-1-[4-(甲硫基)苯基]-
  参考文献：
  名称：

  Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine

  摘要：

  芳基融合和杂环融合的2,4-二氮杂环化合物的化学式为XXXVI，苯二氮杂环化合物的化学式为XXX，苯二氮杂环化合物的化学式为II，Δ-氨基酰胺的化学式为III，芳基二甲胺的化学式为XXXVII，其中A为芳基或杂环环；R.sup.1为氢、烷基、芳基或杂环基；R.sup.2为氢、烷基、取代烷基或芳基；R.sup.3为烷基、芳基、芳基烷基或杂原子取代的烷基或芳基；R.sup.4为氢或烷基；R.sup.5为氢、烷基、芳基或杂环基；R.sup.6为氢、烷基、烷氧基、卤素或融合苯环；R.sup.9为氢、烷基或取代烷基；R.sup.10为氢、烷基或取代烷基。该发明还涉及制备过程、含有药物组合物的制药组合物以及使用化合物XXXVI、XXX、II、III和XXXVII治疗心律失常的方法。

  公开号：

  US05380721A1

文献信息

• Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine
  申请人：Sterling Winthrop Inc.

  公开号：US05380721A1

  公开（公告）日：1995-01-10

  Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II ##STR1## .delta.-aminoamides of formula III and aryldimethanamines of formula XXXVII ##STR2## wherein A is an aryl or hetaryl ring; R.sup.1 is hydrogen, alkyl, aryl or hetaryl; R.sup.2 is hydrogen, alkyl, substituted alkyl, or aryl; R.sup.3 is alkyl, aryl, aralkyl or heteroatom substituted alkyl or aralkyl; R.sup.4 is hydrogen or alkyl; R.sup.5 is hydrogen, alkyl, aryl or hetaryl; R.sup.6 is hydrogen, alkyl, alkoxy, halogen or a fused benzene ring; R.sup.9 is hydrogen, alkyl, or substituted alkyl; and R.sup.10 is hydrogen, alkyl, or substituted alkyl. The invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulas XXXVI, XXX, II, III, and XXXVII.

  芳基融合和杂环融合的2,4-二氮杂环化合物的化学式为XXXVI，苯二氮杂环化合物的化学式为XXX，苯二氮杂环化合物的化学式为II，Δ-氨基酰胺的化学式为III，芳基二甲胺的化学式为XXXVII，其中A为芳基或杂环环；R.sup.1为氢、烷基、芳基或杂环基；R.sup.2为氢、烷基、取代烷基或芳基；R.sup.3为烷基、芳基、芳基烷基或杂原子取代的烷基或芳基；R.sup.4为氢或烷基；R.sup.5为氢、烷基、芳基或杂环基；R.sup.6为氢、烷基、烷氧基、卤素或融合苯环；R.sup.9为氢、烷基或取代烷基；R.sup.10为氢、烷基或取代烷基。该发明还涉及制备过程、含有药物组合物的制药组合物以及使用化合物XXXVI、XXX、II、III和XXXVII治疗心律失常的方法。
• 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
• 4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: A Novel Class III Antiarrhythmic Agents
  作者：Robert E. Johnson、Paul J. Silver、Russell Becker、Nancy C. Birsner、Eric A. Bohnet、G. Maurice Briggs、Carl A. Busacca、Paul Canniff、Philip M. Carabateas、Thomas D'Ambra、Ronald L. Dundore、Jen-Sen Dung、Christopher C. Chadwick、Alan M. Ezrin、William Gorczyca、Peter G. Habeeb、Patrick Horan、Douglas S. Krafte、Gary Pelling、Bernard O'Connor、Manohar T. Saindane、Donald C. Schlegel、Gerald P. Stankus、John Swestock、Walter A. Volberg

  DOI：10.1021/jm00014a008

  日期：1995.7

  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.