[7-氯-5-(2-氯苯基)-3H-1,4-苯并二氮杂-2-基]肼 | 40070-48-2

• 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: [7-氯-5-(2-氯苯基)-3H-1,4-苯并二氮杂-2-基]肼
• 英文名称: 7-chloro-5-(o-chlorophenyl)-2-hydrazino-3H-1,4-benzodiazepine
• 英文别名: 7-chloro-5-(2-chloro-phenyl)-1,3-dihydro-benzo[e][1,4]diazepin-2-one hydrazone；7-chloro-5-(o-chlorophenyl)-3H-1,4-benzodiazepin-2-yl hydrazine；7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine；7-Chlor-5-(2-chlorphenyl)-3H-1,4-benzodiazepin-2-yl-hydrazin；7-Chloro-5-(2-chlorophenyl)-2-hydrazinyl-3H-1,4-benzodiazepine；[7-chloro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2-yl]hydrazine
• CAS: 40070-48-2；112393-63-2
• 化学式: C₁₅H₁₂Cl₂N₄
• 分子量: 319.193
• InChiKey: VTGZNHLCFHSBQH-UHFFFAOYSA-N

物化性质

• 沸点：
  468.7±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  62.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [7-氯-5-(2-氯苯基)-3H-1,4-苯并二氮杂-2-基]肼 在 一水合肼 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 21.9h， 生成 1-(2-aminoethyl)-8-chloro-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

• Triazinobenzodiazepines
  申请人：The Upjohn Company

  公开号：US04028356A1

  公开（公告）日：1977-06-07

  Compounds of formula IV: ##STR1## wherein R and R.sub.2 are hydrogen or methyl; wherein R.sub.1 is --COOH, --COOR' in which R' is alkyl of 1 to 3 carbon atoms, inclusive, --(CnH.sub.2 n)A in which n is an integer of 1 to 3 and A is fluoro, chloro, bromo, trifluoromethyl, hydroxy, alkoxy, in which the alkyl group is defined as above, or ##STR2## in which R" and R'" are hydrogen or alkyl as defined above or together ##STR3## is pyrrolidino, piperidino, morpholino, 4-methylpiperazino, 4-(2-hydroxyethyl)-piperazino; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl, or nitro; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, or 2-pyridyl, are produced. The compounds of formula IV of this invention are sedatives, tranquilizers and muscle-relaxants and can be used for such purposes in mammals and birds.

  IV式化合物：##STR1##其中R和R.sub.2为氢或甲基；其中R.sub.1为--COOH，--COOR'，其中R'为1至3个碳原子的烷基，包括，--(CnH.sub.2 n)A，其中n为1至3的整数，A为氟、氯、溴、三氟甲基、羟基、烷氧基，其中烷基团如上所定义，或##STR2##其中R"和R'"为如上所定义的氢或烷基，或一起##STR3##为吡咯啉基、哌啶基、吗啉基、4-甲基哌嗪基、4-(2-羟乙基)-哌嗪基；其中R.sub.3为氢、氟、氯、溴、三氟甲基或硝基；Ar为苯基、邻氯苯基、邻氟苯基、2,6-二氟苯基或2-吡啶基。本发明的IV式化合物是镇静剂、安定剂和肌肉松弛剂，可用于哺乳动物和鸟类。
• 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。
• S-Substituted derivatives of 8-chloro-6-(2-chlorophenyl)-1-mercaptomethyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine; Synthesis and pharmacology
  作者：Zdeněk J. Vejdělek、Jan Metyš、Miroslav Protiva

  DOI：10.1135/cccc19830123

  日期：——

  Reactions of 7-chloro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-thione (XVIII) and its 5-(2-chlorophenyl) analogue XIX with hydrazines of methylthio-, ethylthio-, cyclohexylthio-, phenylthio-, 4-tolylthio-, 4-chlorophenylthio-, benzylthio-, S-(2-dimethylaminoethyl)thio-, 2-furfurylthio- and 3-pyridylmethylthioacetic acid in boiling butanol gave substance VII and the title compounds VIII-XVII. The synthesis of hydrazines XXVIII-XXXII is described. The compounds prepared are very little toxic, have strong discoordinating activity and are very potent as anticonvulsant agents. In this line they are substantially more active than alprazolam (II) and are not far behind triazolam (III).

  7-氯-5-苯基-1,3-二氢-1,4-苯并二氮杂硫杂环己烯-2-硫酮（XVIII）及其5-(2-氯苯基)类似物XIX与甲硫基、乙硫基、环己硫基、苯硫基、对甲苯硫基、对氯苯硫基、苄硫基、S-(2-二甲氨基乙基)硫基、2-呋喃基硫基和3-吡啶甲基硫基乙酸的肼在沸腾的丁醇中反应，得到物质VII和标题化合物VIII-XVII。描述了肼XXVIII-XXXII的合成。制备的化合物毒性很小，具有强烈的去协调活性，并且作为抗惊厥药物非常有效。在这方面，它们比阿普唑仑（II）活性更高，并且与三唑安定（III）相差无几。
• Triazino benzodiazepines
  申请人：The Upjohn Company

  公开号：US04016165A1

  公开（公告）日：1977-04-05

  Compounds of formula IV: ##STR1## wherein R and R.sub.1 are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen or methyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl or nitro; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl or 2-pyridyl, are produced by reacting a hydrazino compound of the formula I ##STR2## wherein R.sub.2, R.sub.3, and Ar are defined as above, with a carbonyl reagent of the formula II: ##STR3## wherein R and R.sub.1 are defined as above and Y is chloro, bromo, iodo or --O--SO.sub.2 --R.sub.4 in which R.sub.4 is alkyl, defined as above, phenyl, or tolyl, to give the compound III: ##STR4## wherein R, R.sub.1, R.sub.2, R.sub.3, Ar, and Y are defined as above and heating compound III, in an inert organic solvent, to give compound IV above. The compounds of formula IV of this invention and the pharmacologically acceptable acid addition salts thereof are sedatives, tranquilizers and muscle-relaxants and can be used for such purposes in mammals and birds.

  根据上述描述，公式IV的化合物如下所示：其中R和R.sub.1为氢或1至3个碳原子的烷基；其中R.sub.2为氢或甲基；其中R.sub.3为氢、氟、氯、溴、三氟甲基或硝基；Ar为苯基、邻氯苯基、邻氟苯基、2,6-二氟苯基或2-吡啶基，通过将公式I的肼基化合物与公式II的羰基试剂反应而制备：其中R.sub.2、R.sub.3和Ar如上所述，公式II的羰基试剂如下：其中R和R.sub.1如上所述，Y为氯、溴、碘或--O--SO.sub.2 --R.sub.4，其中R.sub.4为烷基、苯基或甲苯基，得到化合物III：其中R、R.sub.1、R.sub.2、R.sub.3、Ar和Y如上所述，将化合物III在惰性有机溶剂中加热，得到上述的化合物IV。本发明的公式IV的化合物及其药理学可接受的酸盐为镇静剂、安定剂和肌肉松弛剂，可用于哺乳动物和鸟类。
• As-triazinobenzodiazepin-1-ones
  申请人：The Upjohn Company

  公开号：US04017492A1

  公开（公告）日：1977-04-12

  Compounds of the formula IV: ##STR1## wherein R.sub.o is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, --C.sub.n H.sub.2n OR in which n is an integer of 1 to 3, inclusive, and R is hydrogen or methyl, ##STR2## in which n is defined as above, and R.sub.6 and R.sub.7 are hydrogen or alkyl as defined above, or together ##STR3## is pyrrolidino, piperidino, morpholino or ##STR4## in which R.sub.8 is methyl, ethyl, or 2-hydroxyethyl, ##STR5## in which m is an integer of 0 to 3, inclusive, and R.sub.9 is hydrogen, lower alkyl of from 1 to 3 carbon atoms, inclusive, wherein R.sub.1 is hydrogen or methyl; wherein R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, or 2-pyridyl; and wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl, or nitro. The compounds of formula IV and the pharmacologically acceptable acid addition salts thereof have sedative, tranquilizing, anticonvulsive and muscle-relaxant activity and can thus be used to produce sedation and tranquilization in mammals, including man, and birds.

  IV式化合物：##STR1##其中R.sub.o为氢，1至3个碳原子的烷基，包括，--C.sub.n H.sub.2n OR，其中n为1至3的整数，且R为氢或甲基，##STR2##其中n定义如上，且R.sub.6和R.sub.7为氢或如上定义的烷基，或者一起##STR3##是吡咯啉，哌啶，吗啉或##STR4##其中R.sub.8为甲基，乙基或2-羟乙基，##STR5##其中m为0至3的整数，且R.sub.9为氢，1至3个碳原子的低烷基，包括，其中R.sub.1为氢或甲基；其中R.sub.2为苯基，o-氯苯基，o-氟苯基，2,6-二氟苯基，或2-吡啶基；其中R.sub.3为氢，氟，氯，溴，三氟甲基，或硝基。IV式化合物及其药理学上可接受的酸盐具有镇静、安定、抗惊厥和肌肉松弛活性，因此可用于在哺乳动物，包括人类和鸟类中产生镇静和安定作用。