8-氯-1-甲基-5-(4-甲基哌嗪-1-基)-6-苯基-[1,2,4]三唑并[4,3-a][1,5]苯并二氮杂卓 | 153901-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 8-氯-1-甲基-5-(4-甲基哌嗪-1-基)-6-苯基-[1,2,4]三唑并[4,3-a][1,5]苯并二氮杂卓
• 英文名称: RL 218
• 英文别名: 8-Chloro-1-methyl-5-(4-methylpiperazin-1-yl)-6-phenyl-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine
• CAS: 153901-56-5
• 化学式: C₂₂H₂₃ClN₆
• 分子量: 406.918
• InChiKey: IVTYOJOLKCTFCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  40.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-氯-1-甲基-5-(4-甲基哌嗪-1-基)-6-苯基-[1,2,4]三唑并[4,3-a][1,5]苯并二氮杂卓 在 acidic solution 作用下， 反应 1.0h， 生成 8-chloro-1-methyl-6-phenyl-4H-<1,2,4>triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one
  参考文献：
  名称：

  酸催化的5-（二烷基氨基）-和5-（烷硫基）取代的8-氯-6-苯基-6H- [1,2,4]三唑[4,3-a] [的苯并二氮杂类性质1,5]苯二氮卓类在小鼠中。

  摘要：

  已经研究了两种苯并二氮杂卓化合物的体外和体内水解作用，以评估它们在小鼠中的体内活性。化合物RL 218和RL 236，被选作N，N-二烷基-8-氯-6-苯基-6H- [1,2,4]三唑[4,3-a] [1,5]苯并二氮杂epi的代表性实例将-5-胺（1）及其5-（烷硫基）取代的类似物（2）快速水解为相应的8-氯-6-苯基-4H- [1,2,4]三唑[4,3- pH值为1.5的酸性水溶液中的a] [1,5]苯并二氮杂-5-5（6H）-one 3（RL 214）。当口服但不腹膜内给予化合物RL 218和RL 236时，该反应在小鼠中也广泛发生。仅当口服时，这两种化合物均具有抗戊四唑诱导的小鼠致命性惊厥的活性。服用药理有效的口服剂量（ED50，可保护50％的小鼠的剂量）后，在评估抗戊四唑活性时，RL 218和RL 236的平均脑浓度低于分析程序的灵敏度极限，而其代谢产物RL 214的脑浓度与口服等剂量剂量的RL

  DOI：

  10.1111/j.2042-7158.1998.tb07132.x
• 作为产物：
  描述：

  8-chloro-4-(dimethylamino)-1,3-dihydro-1-phenyl-2H-1,5-benzodiazepin-2-one 在 劳森试剂 、 氢氧化钾 、 diphenyl ether-biphenyl eutectic 、 苄基三乙基氯化铵 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 氯苯 为溶剂， 反应 26.5h， 生成 8-氯-1-甲基-5-(4-甲基哌嗪-1-基)-6-苯基-[1,2,4]三唑并[4,3-a][1,5]苯并二氮杂卓
  参考文献：
  名称：

  1,5-Benzodiazepines XI. 5-(Dialkylamino) or 5-(alkylthio) substituted 8-chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines with anticonvulsant activity

  摘要：

  The cyclocondensation of (dimethylamino)benzodiazepinones 3a,b with hydrazides yielded triazolobenzodiazepinones 4 which were treated with Lawesson's reagent to give thiolactams 5. The phase-transfer catalyzed (TEBA) alkylation of compounds 5 with suitable alkyl halides afforded 5-(alkylthio)-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines 6a-f. The desired N,N-dialkyl-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines 7a-k were finally obtained from the reaction of the (methylthio)derivatives 6a-d with proper dialkylamines. Compounds 6b-f and 7a-e, g-k were screened for anticonvulsant activity after a preliminary evaluation of their gross behavioral effects and acute toxicity. Nine of the 15 triazolobenzodiazepines tested exerted a clear-cut anticonvulsant effect associated with low acute toxicity. In particular, the most active compounds 6e, f and 7h showed LD50/ED50 ratios that were notably higher than that of phenobarbital and ranging from 50% to 20% of that of diazepam, the latter used as reference drugs.

  DOI：

  10.1016/0223-5234(93)90088-v

文献信息

• 1,5-Benzodiazepines XI. 5-(Dialkylamino) or 5-(alkylthio) substituted 8-chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines with anticonvulsant activity
  作者：GC Grossi、M Di Braccio、G Roma、M Ghia、G Brambilla

  DOI：10.1016/0223-5234(93)90088-v

  日期：1993.1

  The cyclocondensation of (dimethylamino)benzodiazepinones 3a,b with hydrazides yielded triazolobenzodiazepinones 4 which were treated with Lawesson's reagent to give thiolactams 5. The phase-transfer catalyzed (TEBA) alkylation of compounds 5 with suitable alkyl halides afforded 5-(alkylthio)-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines 6a-f. The desired N,N-dialkyl-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines 7a-k were finally obtained from the reaction of the (methylthio)derivatives 6a-d with proper dialkylamines. Compounds 6b-f and 7a-e, g-k were screened for anticonvulsant activity after a preliminary evaluation of their gross behavioral effects and acute toxicity. Nine of the 15 triazolobenzodiazepines tested exerted a clear-cut anticonvulsant effect associated with low acute toxicity. In particular, the most active compounds 6e, f and 7h showed LD50/ED50 ratios that were notably higher than that of phenobarbital and ranging from 50% to 20% of that of diazepam, the latter used as reference drugs.
• Acid-catalysed Hydrolysis and Benzodiazepine-like Properties of 5-(Dialkylamino)- and 5-(Alkylthio)-substituted 8-Chloro-6-phenyl-6<i>H</i>-[1,2,4]triazolo[4,3-<i>a</i>][l,5]benzodiazepines in Mice
  作者：Silvio Caccia、Giancarlo Grossi、Claudia Fracasso、Angelo Nacca、Alfredo Cagnotto、Tiziana Mennini、Marco Ghia、Giorgio Roma

  DOI：10.1111/j.2042-7158.1998.tb07132.x

  日期：2011.4.12

  of two benzodiazepine compounds has been studied to evaluate their in-vivo activity in mice. Compounds RL 218 and RL 236, selected as representative examples of N,N-dialkyl-8-chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiaz epin-5-amines (1) and of their 5-(alkylthio) substituted analogues (2), were rapidly hydrolysed to the corresponding 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H

  已经研究了两种苯并二氮杂卓化合物的体外和体内水解作用，以评估它们在小鼠中的体内活性。化合物RL 218和RL 236，被选作N，N-二烷基-8-氯-6-苯基-6H- [1,2,4]三唑[4,3-a] [1,5]苯并二氮杂epi的代表性实例将-5-胺（1）及其5-（烷硫基）取代的类似物（2）快速水解为相应的8-氯-6-苯基-4H- [1,2,4]三唑[4,3- pH值为1.5的酸性水溶液中的a] [1,5]苯并二氮杂-5-5（6H）-one 3（RL 214）。当口服但不腹膜内给予化合物RL 218和RL 236时，该反应在小鼠中也广泛发生。仅当口服时，这两种化合物均具有抗戊四唑诱导的小鼠致命性惊厥的活性。服用药理有效的口服剂量（ED50，可保护50％的小鼠的剂量）后，在评估抗戊四唑活性时，RL 218和RL 236的平均脑浓度低于分析程序的灵敏度极限，而其代谢产物RL 214的脑浓度与口服等剂量剂量的RL