8-chloro-β-(4-methoxyphenyl)-N,N-dimethyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-ethanamine

• 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: 8-chloro-β-(4-methoxyphenyl)-N,N-dimethyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-ethanamine
• 英文别名: 2-(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-2-(4-methoxyphenyl)-N,N-dimethylethanamine
• 化学式: C₂₇H₂₆ClN₅O
• 分子量: 471.989
• InChiKey: VVFNYRAVIZHBRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine 在 溶剂黄146 、 乙酰氯 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 8-chloro-β-(4-methoxyphenyl)-N,N-dimethyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-ethanamine
  参考文献：
  名称：

  1-(2-Aminoethyl)-6-aryl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity

  摘要：

  A series of 1-(2-amino-1-phenylethyl)-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared and evaluated for diuretic activity. These compounds have diuretic and natriuretic activity but no kaliuretic activity when evaluated by oral administration to the conscious rat. The structure requirements for this activity are discussed. In particular it was found that the 2-aminoethyl side chain at C-1 with hydrogen or methyl substituents on the amino group was required for diuretic activity. A substituent at C-8 was also required; soft substituents such as methylthio and iodo at this position favored activity. Compounds with both phenyl and 2-pyridyl substituents at C-6 were active; substituents on the C-6 phenyl, however, reduced or eliminated the activity. Substituents other than phenyl at the 1-position of the 2-aminoethyl side chain were detrimental to activity; phenyl substitution at this position was required for activity when the substituent at C-8 was chloro but not when it was bromo.

  DOI：

  10.1021/jm00126a003

文献信息

• 1-Ethanamine-triazolo-benzodiazepines as diuretics
  申请人：The Upjohn Company

  公开号：US04514407A1

  公开（公告）日：1985-04-30

  Triazolo-benzodiazepine-1-ethanamines of the formulas ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Ring A are as defined in the specification, e.g., 8-chloro-N,N-dimethyl-.beta.,6-diphenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benz odiazepine-1-ethanamine, and pharmacologically acceptable salts thereof, have been found to have substantial diuretic, natriuretic, but little, if any, kaliuretic activity, which can be used alone, or concomittently with other diuretic drugs such as furosemide or hydrochlorothiazide and/or with antihypertensive agents such as propranolo, captopril, minoxidil, prazosin, guanadrel sulfate, whose actions are supplemented by the action of a diuretic drug.

  Triazolo-苯二氮卓-1-乙胺的分子式为##STR1##其中R、R.sub.1、R.sub.2、R.sub.3、R.sub.4和环A如规范中所定义，例如8-氯-N，N-二甲基-β，6-二苯基-4H-[1,2,4]三唑并[4,3-a][1,4]苯二氮卓-1-乙胺及其药理学上可接受的盐，已被发现具有显著的利尿、排钠作用，但几乎没有钾排泄作用，可单独使用，或与其他利尿药物如呋塞米或氢氯噻嗪以及/或抗高血压药物如普萘洛尔、卡普托普利、米诺地尔、普拉唑辛、瓜那德雷酸盐同时使用，其作用被利尿药物的作用所补充。
• US4514407A
  申请人：——

  公开号：US4514407A

  公开（公告）日：1985-04-30
• US4689413A
  申请人：——

  公开号：US4689413A

  公开（公告）日：1987-08-25
• 1-(2-Aminoethyl)-6-aryl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity
  作者：Jackson B. Hester、James H. Ludens、D. Edward Emmert、Bruce E. West

  DOI：10.1021/jm00126a003

  日期：1989.6

  A series of 1-(2-amino-1-phenylethyl)-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared and evaluated for diuretic activity. These compounds have diuretic and natriuretic activity but no kaliuretic activity when evaluated by oral administration to the conscious rat. The structure requirements for this activity are discussed. In particular it was found that the 2-aminoethyl side chain at C-1 with hydrogen or methyl substituents on the amino group was required for diuretic activity. A substituent at C-8 was also required; soft substituents such as methylthio and iodo at this position favored activity. Compounds with both phenyl and 2-pyridyl substituents at C-6 were active; substituents on the C-6 phenyl, however, reduced or eliminated the activity. Substituents other than phenyl at the 1-position of the 2-aminoethyl side chain were detrimental to activity; phenyl substitution at this position was required for activity when the substituent at C-8 was chloro but not when it was bromo.