(8-chloro-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-ylmethyl)-diethyl-amine | 37115-31-4

• 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-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-ylmethyl)-diethyl-amine
• 英文别名: 8-chloro-1-[(diethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine；1-<(Diethylamino)methyl>-6-phenyl-8-chlor-4H-s-triazolo<4.3-a><1.4>benzodiazepin；8-chloro-1-[(diethyl amino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine；N-[(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methyl]-N-ethylethanamine
• CAS: 37115-31-4
• 化学式: C₂₁H₂₂ClN₅
• 分子量: 379.892
• InChiKey: NUSHELRLSJLWBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine 在 potassium iodide 作用下， 以 四氢呋喃 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.91h， 生成 (8-chloro-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-ylmethyl)-diethyl-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

文献信息

• Intermediates and process for the production of certain
  申请人：The Upjohn Company

  公开号：US03947466A1

  公开（公告）日：1976-03-30

  A multi-step process for the preparation of 1-[(amino - or substituted amino)methyl]-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepines of the formula VI: ##SPC1## wherein R' is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, and wherein the rings A and B are unsubstituted or substituted by one or two substituents selected from the group consisting of chloro, fluoro, bromo, nitro, and trifluoromethyl, which comprises: treating a compound of the formula I: ##SPC2## wherein rings A and B are defined as above, with acetic anhydride and formic acid to obtain compound II: ##SPC3## wherein A and B rings have the significance as above, treating compound II with sufficient formaldehyde to produce compound III, the 3,5-bis(hydroxymethyl)derivative of II; treating III with phthalimide, triphenylphosphine and diethyl azodicarboxylate to give compound IV, the 3,5-bis(phthalimidomethyl) derivative of II; and treating IV with hydrazine hydrate to obtain a compound of formula V ##SPC4## wherein rings A and B are defined, as herein above. Compound V can then be alkylated in known manner to give those compounds of formula VIa which corresponds to formula VI when R' is desired to be alkyl. The compounds of formula VI have antidepressant and antianxiety effects in mammals and birds.

  一种用于制备公式VI中1-[(氨基或取代氨基)甲基]-6-苯基-4H-s-三唑并[4,3-a][1,4]苯二氮杂平的多步骤过程：其中R'是氢或含有1至3个碳原子的烷基，环A和环B未取代或取代为来自氯、氟、溴、硝基和三氟甲基的一个或两个取代基，包括以下步骤：将公式I的化合物：用乙酸酐和甲酸处理以获得化合物II；将化合物II与足够的甲醛处理以产生化合物III，II的3,5-双(羟甲基)衍生物；将III与邻苯二甲酰亚胺、三苯基膦和双乙酰双氨基甲酸酯处理以给出化合物IV，II的3,5-双(邻苯二甲酰亚胺基)衍生物；将IV与水合肼处理以获得公式V的化合物，其中A和B环如上定义。然后，可以以已知方式烷基化化合物V，以给出当R'需要是烷基时对应于公式VI的公式VIa的那些化合物。公式VI的化合物在哺乳动物和鸟类中具有抗抑郁和抗焦虑作用。
• Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][
  申请人：The Upjohn Company

  公开号：US03957761A1

  公开（公告）日：1976-05-18

  A multistep process for the production of a compound of the formula V: ##SPC1## wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive or together ##EQU1## is pyrrolidino, piperidino, 4-methylpiperazino or morpholino; and wherein the rings A and B are unsubstituted, or substituted by one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro and trifluoromethyl, which comprises treating an equivalent of a compound of formula 1: ##SPC2## Wherein rings A and B are defined as above, with 2 equivalents of an .alpha.-phthalimido acetyl halide in an inert organic solvent to obtain a 1,3-dioxo-2-isoindolineacetic acid, [[N-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamido]methylene]hydrazide II which when treated with trifluoroacetic acid gives compound III; treating compound III with a dialkylmethyleneammonium chloride in an inert organic solvent to obtain a 2-[3-(dialkylamino)methyl-5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benz ophenone IV and treating IV with hydrazine in an alkanol to obtain a compound V above. Also claimed are the intermediates II and IV. The 1-aminomethyltriazolobenzodiazepine compounds (V) are used for treatment of anxieties and/or depressions in mammals and birds.

  一种生产公式V化合物的多步骤过程：##SPC1##其中，R'和R"是包括1至3个碳原子的烷基，或者一起是##EQU1##是吡咯烷基，哌嗪基，4-甲基哌嗪基或吗啉基；环A和B是未取代的或由来自氟、氯、溴、硝基和三氟甲基的一个或多个取代基取代的。该过程包括将化合物1的等量物：##SPC2##其中，环A和B如上所定义，与2当量的α-邻苯二甲酰亚胺酰卤处理在惰性有机溶剂中，以获得1,3-二氧-2-异吲哚乙酸，[[N-(2-苯甲酰苯基)-1,3-二氧-2-异吲哚乙酰胺]亚甲基]腙II，当用三氟乙酸处理II时获得化合物III；将化合物III与二烷基亚甲基氯化铵在惰性有机溶剂中处理，以获得2-[3-(二烷基氨基)甲基-5-(邻苯二甲酰亚胺甲基)-4H-1,2,4-三唑-4-基]苯基酮IV，并将IV用肼在烷基醇中处理，以获得上述化合物V。还声明了中间体II和IV。1-氨甲基三唑苯二氮平化合物（V）用于治疗哺乳动物和鸟类的焦虑和/或抑郁症。
• 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.

  式为：##STR1## 其中R'o和R"o为1至3个碳原子的氢或烷基；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，o-氯苯基，o-氟苯基，2,6-二氟苯基和2-吡啶基，通过多步反应从式为I的化合物制备而成：##STR2## 其中R.sub.1和R.sub.2的定义如上，X为氯或溴。式III的化合物，其制备中间体，化合物IIIA的席夫碱（其中R'o和R"o为氢）和药理学上可接受的酸盐在鸟类和哺乳动物，包括人类中作为镇静剂，抗焦虑，抗抑郁，抗癫痫和肌肉松弛剂有用。
• [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-[(Dialkylamino)met
  申请人：The Upjohn Company

  公开号：US04226772A1

  公开（公告）日：1980-10-07

  The compound of the formula ##STR1## wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive; wherein 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; and wherein R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, or 2,6-difluorophenyl, is prepared by reacting a 1-halomethyl-6-phenyl-4H-s-triazo[4,3-a][1,4]-benzodiazepine with N,N-dimethylhydroxylamine and a strong base. The compound II and its pharmacologically acceptable acid addition salts have sedative and tranquilizing activity.

  化学式为##STR1##的化合物，其中R'和R"是1到3个碳原子的烷基；R.sub.1是氢、氟、氯、溴、硝基、三氟甲基或烷基硫基，其中烷基部分为1到3个碳原子；R.sub.2是苯基、邻氯苯基、邻氟苯基或2,6-二氟苯基。该化合物是通过将1-卤代甲基-6-苯基-4H-s-三唑[4,3-a][1,4]-苯并二氮平与N,N-二甲基羟胺和强碱反应制备而成。化合物II及其药学上可接受的酸盐具有镇静和安眠作用。