8-chloro-1-methyl-6-phenyl-4H-<1,2,4>triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one | 54748-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并二氮卓类
• 英文名称: 8-chloro-1-methyl-6-phenyl-4H-<1,2,4>triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one
• 英文别名: RL 214；8-chloro-1-methyl-6-phenyl-4,6-dihydro-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5-one；8-chloro-4,6-dihydro-1-methyl-6-phenyl-5H-S-triazolo[4,5-a][1,5]benzodiazepin-5-one；8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one；1-Methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]-benzodiazepin-5-one；1-methyl-8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,5]benzodiazepin-5-one；8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-one
• CAS: 54748-06-0
• 化学式: C₁₇H₁₃ClN₄O
• 分子量: 324.769
• InChiKey: XVMDIBGSCXIXJJ-UHFFFAOYSA-N

物化性质

• 熔点：
  297-298 °C(Solv: ethanol (64-17-5))
• 沸点：
  648.0±65.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-chloro-1-methyl-6-phenyl-4H-<1,2,4>triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one 在 劳森试剂 、 氢氧化钾 、 苄基三乙基氯化铵 、 对甲苯磺酸 作用下， 以 氯苯 、 甲苯 为溶剂， 反应 48.5h， 生成 (8-Chloro-1-methyl-6-phenyl-6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-yl)-dimethyl-amine
  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
• 作为产物：
  描述：

  7-chloro-2-methylamino-5-phenyl-4H-3,5-dihydro-1,5-benzodiazepin-4-one 在 三乙胺 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 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：

  1,5-Benzodiazepin-4-ones

  摘要：

  本文披露了一种1,5-苯并二氮平-4-酮衍生物，其在1,2-位置之间带有三唑环。这些1,2-三唑基-1,5-苯并二氮平-4-酮可用作肌肉松弛剂、抗惊厥和镇静剂。

  公开号：

  US04111934A1

文献信息

• 4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04164498A1

  公开（公告）日：1979-08-14

  Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

  以下公式##STR1##的化合物在哺乳动物中作为中枢神经系统抑制剂、镇静剂、安眠药、生长促进剂、抗惊厥剂和肌肉松弛剂方面具有用途。
• 4H-s-Triazolo[4,3-a][1,5]benzodiazepin-5-ones as tranquilizers
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04164580A1

  公开（公告）日：1979-08-14

  Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

  以下化学式的化合物##STR1##在哺乳动物中可用作中枢神经系统抑制剂、镇静剂、安眠药、生长促进剂、抗惊厥药和肌肉松弛剂。
• Novel 4H-S-triazolo[4,3-A] [1,5]benzodiazepin-5-ones
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04213982A1

  公开（公告）日：1980-07-22

  Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

  以下公式的化合物##STR1##在哺乳动物物种中可用作中枢神经系统抑制剂、镇静剂、催眠剂、生长促进剂、抗痉挛剂和肌肉松弛剂。
• S-triazolo-1,5-benzodiazpine-4-ones
  申请人：The Upjohn Company

  公开号：US04075202A1

  公开（公告）日：1978-02-21

  A s-triazolo-1,5-benzodiazepin-4-one selected from the group of compounds of the formulae: ##STR1## wherein R.sub.o is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, hydroxy, hydroxymethyl, and ##STR2## in which R" and R'" are hydrogen or alkyl defined as above, or together ##STR3## is selected from the group consisting of pyrrolidino, piperidino, morpholino, and N-methylpiperazino; wherein R is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive and ##STR4## in which R" and R'" are hydrogen or alkyl as defined above or together ##STR5## is defined as above; wherein R.sub.1 is hydrogen or methyl; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl alkyl defined as above, halogen, nitro, trifluoromethyl, and alkylthio in which alkyl is defined as above are produced from the corresponding 4-hydrazino-2H-1,5-benzodiazepines-2-ones of the formula (11A) ##STR6## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 have the significance of above, with an acetic acid chloride or if R.sub.o is hydrogen with ethyl ortho-formate, and heating to an elevated temperature to give the corresponding 4H-s-triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one which by additional procedures can be converted to the various compounds presented by formula 111A. Compounds of formula 111B are best obtained by reacting a 4-thio-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione (1A) ##STR7## with a selected carbazate, followed by heating to an elevated level. Additional steps are necessary to synthesize the various compounds presented by formula 111B. The new compounds of formula 111A and 111B have tranquilizing and sedative activity.

  从下列式中选择一种s-三唑并[1,5]苯二氮平-4-酮化合物：##STR1##其中R.sub.o为氢、1至3个碳原子的烷基、羟基、羟甲基和##STR2##其中R"和R'"为氢或上述定义的烷基，或者一起##STR3##从吡咯烷基、哌啶基、吗啉基和N-甲基哌嗪基中选择；其中R为氢、1至3个碳原子的烷基和##STR4##其中R"和R'"为上述定义的氢或烷基，或者一起##STR5##如上所述定义；其中R.sub.1为氢或甲基；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、三氟甲基和硫代烷基中选择，其中烷基如上所述，由相应的式(11A)的4-肼基-2H-1,5-苯并二氮平-2-酮##STR6##其中R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5具有上述意义，与乙酸氯或如果R.sub.o为氢，则与乙酸乙酯酸酐反应，并加热至高温，以得到相应的4H-s-三唑并[4,3-a][1,5]苯并二氮平-5(6H)-酮，通过其他步骤可以将其转化为公式111A所示的各种化合物。公式111B的化合物最好是通过将4-硫代-1H-1,5-苯并二氮平-2,4-(3H,5H)-二酮(1A)##STR7##与选择的卡巴肼反应，然后加热至高温来获得的。需要其他步骤来合成公式111B所示的各种化合物。公式111A和111B的新化合物具有镇静和催眠作用。
• 4H-S-Triazolo[4,3-2][1,5]benzodiazepin-5-ones
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04133809A1

  公开（公告）日：1979-01-09

  Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

  以下化合物的公式##STR1##在哺乳动物物种中作为中枢神经系统抑制剂、镇静剂、安眠药、促进生长剂、抗惊厥剂和肌肉松弛剂是有用的。