8-chloro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine | 54304-87-9

• 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-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine
• 英文别名: 8-chloro-6-(o-chlorophenyl)-1-(chloromethyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine；8-Chloro-1-(chloromethyl)-6(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine；8-chloro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo-[4,3-a][1,4]benzodiazepine；8-chloro-1-(chloromethyl)-6-(2-chlorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
• CAS: 54304-87-9
• 化学式: C₁₇H₁₁Cl₃N₄
• 分子量: 377.66
• InChiKey: IIAYCZQHYRCWGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-甲基炔丙基胺 、 8-chloro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine 在 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以62%的产率得到N-[[8-chloro-6-(2-chlorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]methyl]-N-methylprop-2-yn-1-amine
  参考文献：
  名称：

  1-（氨基烷基）-6-芳基-4-Hs-三唑并[4,3-a] [1,4]苯并二氮杂卓具有抗焦虑和抗抑郁活性。

  摘要：

  已经制备了一系列的1-（氨基烷基）-6-芳基-4H-s-三唑并[4，3-a] [1，4]苯并二氮杂并评估中枢神经系统活性。我们发现该系列的成员在旨在检测抗焦虑和抗抑郁活性的药理学测试系统中具有活性。每种类型的活性可以通过适当的取代基选择独立地变化。

  DOI：

  10.1021/jm00178a009
• 作为产物：
  描述：

  [7-氯-5-(2-氯苯基)-3H-1,4-苯并二氮杂-2-基]肼 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 1.91h， 生成 8-chloro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine
  参考文献：
  名称：

  1-（氨基烷基）-6-芳基-4-Hs-三唑并[4,3-a] [1,4]苯并二氮杂卓具有抗焦虑和抗抑郁活性。

  摘要：

  已经制备了一系列的1-（氨基烷基）-6-芳基-4H-s-三唑并[4，3-a] [1，4]苯并二氮杂并评估中枢神经系统活性。我们发现该系列的成员在旨在检测抗焦虑和抗抑郁活性的药理学测试系统中具有活性。每种类型的活性可以通过适当的取代基选择独立地变化。

  DOI：

  10.1021/jm00178a009

文献信息

• 1-Halomethyl-6-phenyl-4H-s-[4,3-a][1,4]benzodiazepines
  申请人：The Upjohn Company

  公开号：US04141902A1

  公开（公告）日：1979-02-27

  1-Substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula II: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, methyl, ethyl, fluorine, chlorine, and bromine, and X is selected from fluorine, chlorine, and bromine; wherein R.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms inclusive; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl, as defined above, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, and alkylsulfonyl, in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are prepared by reacting a compound of the formula: ##STR2## wherein R.sub.1, R.sub.2, R.sub.3 R.sub.4, and R.sub.5 are defined as above, with an haloacyl chloride or haloacyl bromide of the formula ##STR3## wherein R.sub.o and X are defined as above and X' is chlorine or bromine. The new products of formula II including their pharmacologically acceptable acid addition salts are useful as sedatives, tranquilizers and muscle relaxants in mammals and birds, and if X.dbd.X".dbd.Cl or Br they are useful as intermediates for cyano, alkylthio and dialkylamino products of high sedative and tranquilizing activity.

  式II的1-取代-6-苯基-4H-s-三唑并[4,3-a][1,4]苯二氮杂环戊烷化合物：其中R.sub.0从氢、甲基、乙基、氟、氯和溴组成的群体中选择，X从氟、氯和溴中选择；其中R.sub.1从氢、1至3个碳原子的包括的烷基中选择；其中R.sub.2、R.sub.3、R.sub.4和R.sub.5从氢、如上定义的烷基、卤素、硝基、氰基、三氟甲基和烷氧基、烷硫基、烷硫醇基和烷磺酰基组成的群体中选择，其中碳链基团为1至3个碳原子，包括，通过将式化合物反应得到：其中R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5如上定义，与式卤代酰氯或卤代酰溴反应得到：其中R.sub.o和X如上定义，X'为氯或溴。包括其药理学上可接受的酸盐的式II的新产物可用作哺乳动物和鸟类的镇静剂、安定剂和肌肉松弛剂，如果X.dbd.X".dbd.Cl或Br，则它们可用作具有高镇静和安定活性的氰基、烷硫基和二烷基胺产物的中间体。
• 1-[(Allylamino)-methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines
  申请人：The Upjohn Company

  公开号：US04021441A1

  公开（公告）日：1977-05-03

  Compounds of the formula II: ##STR1## wherein R is cyclopropyl, cyclopropylmethyl, or allyl; wherein R', R", and R.sub.1 are hydrogen or alkyl of 1 to 3 carbon atoms inclusive; and wherein R.sub.2, R.sub.3, and R.sub.4 are hydrogen, alkyl as defined above, fluoro, chloro, bromo, nitro, trifluoromethyl, or alkylthio in which alkyl is defined as above, are prepared by reacting a compound of the formula I. ##STR2## wherein R", R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are defined as above, and wherein X is chlorine or bromine, with an amine of the formula ##STR3## wherein R and R' are defined as above. The compounds of formula II and the pharmacologically acceptable acid salts thereof have tranquilizing, sedative, antianxiety, and anticonvulsant activity and can be used in animals and birds.

  公式II的化合物：其中R为环丙基、环丙基甲基或烯丙基；其中R'、R"和R₁为氢或1至3个碳原子的烷基；其中R₂、R₃和R₄为氢、如上所定义的烷基、氟、氯、溴、硝基、三氟甲基或烷基硫，其中烷基如上定义，通过将公式I的化合物与上述定义的R"、R₁、R₂、R₃和R₄，并且其中X为氯或溴的胺反应制备。公式II的化合物及其药理学上可接受的酸盐具有镇定、镇静、抗焦虑和抗惊厥活性，可用于动物和鸟类。
• 1-[(Aminooxy)-methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4]
  申请人：The Upjohn Company

  公开号：US04009175A1

  公开（公告）日：1977-02-22

  Compounds of the formula: ##STR1## wherein R'o and R"o are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; R.sub.2 is phenyl, o-chlorophenyl, 0-fluorophenyl, 2,6-difluorophenyl and 2-pyridyl are prepared by multistep reactions from compounds of formula I: ##STR2## wherein R.sub.1 and R.sub.2 are defined as above and X is chlorine or bromine. Compounds of formula III, intermediates in the preparation thereof, Schiff's bases of compounds IIIA (III in which R'o and R"o are hydrogen), and the pharmacologically acceptable acid addition salts are useful in birds and mammals, including man, as sedatives, antianxiety, antidepressant, anticonvulsive, and muscular relaxing agents.

  分子式为：##STR1## 其中R'o和R"o为氢或1至3个碳原子的烷基；R.sub.1为氢、氟、氯、溴、硝基、三氟甲基或烷基硫醚，其中烷基部分为1至3个碳原子；R.sub.2为苯基、邻氯苯基、邻氟苯基、2,6-二氟苯基和2-吡啶基，是由分子式I的化合物经多步反应制备而成：##STR2## 其中R.sub.1和R.sub.2如上所定义，X为氯或溴。分子式III的化合物，其制备中间体，化合物IIIA（III中R'o和R"o为氢的席夫碱）以及药理学上可接受的酸加成盐在鸟类和哺乳动物，包括人类中，可用作镇静剂、抗焦虑、抗抑郁、抗癫痫和肌肉松弛剂。
• [3-Substituted-5-[(di-methylamino)methyl]-4H-1,2,4-triazol-
  申请人：The Upjohn Company

  公开号：US04010177A1

  公开（公告）日：1977-03-01

  Compounds of the formula I: ##STR1## wherein R.sub.1 is hydroxymethyl, or -CH.sub.2 NR.sub.6 R.sub.7, in which R.sub.6 is -CH.sub.2 -C.tbd.CH, -CH.sub.2 -CH=CH.sub.2, ##STR2## or alkyl of 1 to 3 carbon atoms, inclusive; R.sub.7 is hydrogen or alkyl of 1 to 3 carbon atoms, or together ##STR3## is pyrrolidino, piperidino or morpholino; wherein R.sub.2 is hydrogen, chlorine or fluorine; wherein R.sub.3 is hydrogen, or fluorine if R.sub.2 is fluorine; wherein R.sub.4 is hydrogen, fluorine, chlorine, bromine, nitro, or trifluoromethyl; and wherein R.sub.5 is hydrogen, methyl or ethyl. These compounds, except those in which R.sub.7 is hydrogen, are produced by heating a compound of formula II: ##STR4## wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are defined as hereinabove, and wherein R'.sub.1 is the same as R.sub.1 except that in defining R'.sub.1,R.sub.7 may not be hydrogen, with aqueous formaldehyde in formic acid solution at reflux temperature (about 100.degree. C.). Compounds in which R.sub.7 are hydrogen require steps further shown in the specification. The compounds of formula I and their pharmacologically acceptable acid addition salts thereof have tranquilizing, anti-anxiety and anti-convulsant activity useful for the treatment of animals and man.

  公式I的化合物：##STR1## 其中R.sub.1是羟甲基或-CH.sub.2 NR.sub.6 R.sub.7，其中R.sub.6是-CH.sub.2 -C.tbd.CH，-CH.sub.2 -CH=CH.sub.2，##STR2##或包括1至3个碳原子的烷基; R.sub.7是氢或包括哒啶基，哌啶基或吗啡啶基; R.sub.2是氢，氯或氟; R.sub.3是氢，如果R.sub.2为氟，则为氟; R.sub.4是氢，氟，氯，溴，硝基或三氟甲基; R.sub.5是氢，甲基或乙基。除了R.sub.7为氢的化合物外，这些化合物是通过将公式II的化合物加热而产生的：##STR4##其中R.sub.2，R.sub.3，R.sub.4和R.sub.5的定义如上所述，而R'.sub.1与R.sub.1相同，但在定义R'.sub.1时，R.sub.7可能不是氢，在甲酸溶液中以回流温度（约100°C）与水甲醛反应。其中R.sub.7为氢的化合物需要在规范中进一步步骤。公式I的化合物及其药理学上可接受的酸加盐具有镇静，抗焦虑和抗惊厥活性，可用于动物和人的治疗。
• 1-(Aminoalkyl)
  申请人：The Upjohn Company

  公开号：US04250094A1

  公开（公告）日：1981-02-10

  1-(Aminoalkyl) substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula II: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, methyl, or ethyl; wherein R' and R" are selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.1 is selected from the group consisting of hydrogen, alkyl as defined above; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl as defined above, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, and alkylsulfonyl, in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are prepared by reacting a compound of the formula: ##STR2## wherein X is chlorine or bromine and wherein R.sub.0, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are defined as above with an amine of the formula: ##STR3## wherein R' and R" are defined as above. The new products of formula II including their pharmacologically acceptable acid addition salts and N-oxides are useful as sedatives, tranquilizers, muscle relaxants and antidepressants in mammals and birds.

  式II中的1-(氨基烷基)取代-6-苯基-4H-s-三唑并[4,3-a][1,4]苯二氮平，其中R.sub.0从氢、甲基或乙基中选择；其中R'和R"从氢和1到3个碳原子的烷基中选择；其中R.sub.1从氢和上述定义的烷基中选择；其中R.sub.2、R.sub.3、R.sub.4和R.sub.5从氢、上述定义的烷基、卤素、硝基、氰基、三氟甲基、烷氧基、烷硫基、烷基亚磺酰基中选择，其中碳链基团为1到3个碳原子，包括通过将式中R.sub.0、R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5定义为上述的化合物与式为： ##STR2## 其中X为氯或溴，R.sub.0、R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5如上所定义，与式为： ##STR3## 其中R'和R"如上所定义的胺反应制备而成。式II的新产品，包括其药理学上可接受的酸盐和N-氧化物，可用作哺乳动物和鸟类的镇静剂、安定剂、肌肉松弛剂和抗抑郁剂。