N-<3-propylamino>-7,8-dimethoxy-2,3,4,5-tetrahydro-2-oxo-1H-3-benzazepin | 161885-40-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-<3-propylamino>-7,8-dimethoxy-2,3,4,5-tetrahydro-2-oxo-1H-3-benzazepin
• 英文别名: 3-[3-(N-benzyl-3,4-dimethoxyanilino)propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one
• CAS: 161885-40-1
• 化学式: C₃₀H₃₆N₂O₅
• 分子量: 504.626
• InChiKey: FZONKRRUXRVVBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<3-propylamino>-7,8-dimethoxy-2,3,4,5-tetrahydro-2-oxo-1H-3-benzazepin 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以93%的产率得到N-<3-N-(3,4-dimethoxyphenyl)propylamino>-7,8-dimethoxy-2,3,4,5-tetrahydro-2-oxo-1H-3-benzazepin
  参考文献：
  名称：

  Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties

  摘要：

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00166-7
• 作为产物：
  描述：

  N-benzyl-3,4-dimethoxyaniline 、 3-(3-氯丙基)-7,8-二甲氧基-2,3,4,5-四氢-1H-3-苯并氮杂卓-2-酮 反应 1.5h， 以40%的产率得到N-<3-propylamino>-7,8-dimethoxy-2,3,4,5-tetrahydro-2-oxo-1H-3-benzazepin
  参考文献：
  名称：

  Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties

  摘要：

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00166-7

文献信息

• ANTI-ARRHYTHMIC N-SUBSTITUTED 3-BENZAZEPINES OR ISOQUINOLINES
  申请人：SMITHKLINE BEECHAM LABORATOIRES PHARMACEUTIQUES

  公开号：EP0700389A1

  公开（公告）日：1996-03-13
• [EN] ANTI-ARRHYTHMIC N-SUBSTITUTED 3-BENZAZEPINES OR ISOQUINOLINES<br/>[FR] 3-BENZAZEPINES OU ISOQUINOLINES N-SUBSTITUEES A ACTION ANTIARYTHMIQUE
  申请人：SMITHKLINE BEECHAM LABORATOIRES PHARMACEUTIQUES

  公开号：WO1994027971A1

  公开（公告）日：1994-12-08

  (EN) A compound of formula (I) or a salt thereof, or a solvate thereof, wherein A represents CH2, (CH2)2, CO, COCH2, CH2CO, CSCH2 or CH=CH; B represents CH2 or CO; Z represents a bond, CH2, (CH2)2 or X-CH2-CH2 wherein X represents O or S; D represents CO, SO2, NH-CO, NH-SO2, CH=CH or P(O)OR6 wherein R6 is C1-6 alkyl; Q represents aryl, aralkyl, aralkenyl or aralkynyl, wherein the aryl moiety may be substituted or unsubstituted with 1 to 5 substituents selected from the list consisting of nitro, halogen, alkylsulfonamide, amino, 1-imidazo, alkyl or haloalkyl, or Q represents substituted or unsubstituted: furanyl, pyranyl, thienyl, thiazolyl, imidazolyl, triazolyl or the benzo fused equivalents of furanyl, pyranyl, thienyl, thiazolyl, imidazolyl or triazolyl, indolyl, oxoindolyl, indenyl, isoindenyl, indazolyl, indolizinyl or pyridinyl or cycloalkyl optionally fused to an aryl group; R1, R2, R3, R4 and R5 each independently represent H, alkyl, OH or alkoxy or, if attached to adjacent carbon atoms, any two of R1, R2, R3, R4 and R5 together with the carbon atoms to which they are attached may form a fused heterocyclic ring of four to six atoms wherein one, two or three of the said atoms are oxygen or nitrogen; and E represents C2-4 n-alkylene group wherein each carbon is optionally substituted by R6; a process for preparing such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.(FR) Composé de la formule (I) ou sel ou solvant de ce composé. Dans cette formule, A représente CH2, (CH2)2, CO, COCH2, CH2CO, CSCH2 ou CH=CH; B représente CH2 ou CO; Z représente une liaison, CH2, (CH2)2 ou X-CH2-CH2 dans lequel X représente O ou S; D représente CO, SO2, NH-CO, NH-SO2, CH=CH ou P(O)OR6, R6 représentant alkyle C1-6; Q représente aryle, aralkyle, aralcényle ou aralkynyle, la fraction aryle étant substituée ou non par 1 à 5 substituants choisis dans la liste composée de nitro, halogène, alkylsulfonamide, amino, 1-imidazo, alkyle ou haloalkyle, ou Q représente furanyle, pyranyle, thiényle, thiazolyle, imidazolyle, triazolyle ou les équivalents benzo-fusionnés de furanyle, pyranyle, thiényle, thiazolyle, imidazolyle ou triazolyle, indolyle, oxoindolyle, indényle, isoindenyle, indazolyle, indolizinyle ou pyridinyle ou cycloalkyle éventuellement fusionné à un groupe aryle, tous substitués ou non substitués; R1, R2, R3, R4 et R5 représentent chacun indépendamment H, alkyle, OH, ou alcoxy ou, s'ils sont accolés à des atomes de carbone adjacents, deux éléments quelconques parmi R1, R2, R3, R4 et R5 forment, avec les atomes de carbone auxquels ils sont accolés, un noyau hétérocyclique fusionné de 4 à 6 atomes parmi lesquels un à trois sont des atomes d'oxygène ou d'azote; et E représente un groupe n-alkylène C2-4 dans lequel chaque atome de carbone est éventuellement substitué par R6. L'invention se rapporte également à un procédé de préparation de ces composés, à des compositions pharmaceutiques les comprenant, ainsi qu'à leur utilisation dans le domaine médical.
• Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties
  作者：Guy Nadler、Jean-François Faivre、Marie-Claire Forest、Brigitte Cheval、Michel Martin、Michel Souchet、Bernard Gout、Antoine Bril

  DOI：10.1016/s0968-0896(98)00166-7

  日期：1998.11

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.