1-(1-benzyloxycarbonyl-4-piperidinyl)-7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one | 93592-55-3

• 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: 1-(1-benzyloxycarbonyl-4-piperidinyl)-7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one
• 英文别名: benzyl 4-[7-chloro-5-(2-fluorophenyl)-2-oxo-3H-1,4-benzodiazepin-1-yl]piperidine-1-carboxylate
• CAS: 93592-55-3
• 化学式: C₂₈H₂₅ClFN₃O₃
• 分子量: 505.976
• InChiKey: NBUYDLLTNLKKJX-UHFFFAOYSA-N

物化性质

• 沸点：
  696.5±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(1-benzyloxycarbonyl-4-piperidinyl)-7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one 在 三氯化铝 、 水 、 potassium carbonate 、 苯甲醚 作用下， 以 硝基甲烷 、 二氯甲烷 、 溶剂黄146 、 乙腈 为溶剂， 反应 37.5h， 生成 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-3-hydroxy-1-(1-methyl-4-piperidinyl)-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  1-Azacycloalkyl-1,4-benzodiazepin-2-ones with antianxiety-antidepressant actions

  摘要：

  A series of 1-azacycloalkyl-1,4-benzodiazepin-2-ones were synthesized from 1-azacycloalkyl-2-benzoylanilines and corresponding imines and then evaluated for their central nervous system activities. Pharmacological data showed that some of these compounds have potent antidepressant properties, as assessed by their antagonism of tetrabenzine (TBZ) induced ptosis and their inhibition of [3H]norepinephrine uptake into rat brain synaptosomes, as well as their moderate antianxiety properties of preventing of pentylenetetrazol (PTZ) convulsion, suppressing conflict behavior, and displacing potential for [3H]diazepam binding. Introduction of a halogen substituent at position 7 of the 1,4-benzodiazepine ring lengthened the anti-PTZ effects, although the peak effect was slightly reduced and clearly enhanced the anti-PTZ and anticonflict properties. Introduction of Cl to the ortho position of the phenyl ring at position 5 greatly reduced the antidepressant properties. The secondary amine function of the azacyclic ring at position 1 was essential for the production of the antidepressant properties. Of these new series, 7-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1-(4-piperidinyl)-2H-1,4-benzodi azepin-2 -one has the potential to become a useful antidepressant drug with a moderate antianxiety property.

  DOI：

  10.1021/jm00383a003
• 作为产物：
  描述：

  4-[4-chloro-2-(2-fluoro-benzoyl)anilino]-1-methylpiperidine 在 盐酸 、 sodium hydroxide 、 碳酸氢铵 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 34.5h， 生成 1-(1-benzyloxycarbonyl-4-piperidinyl)-7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  1-Azacycloalkyl-1,4-benzodiazepin-2-ones with antianxiety-antidepressant actions

  摘要：

  A series of 1-azacycloalkyl-1,4-benzodiazepin-2-ones were synthesized from 1-azacycloalkyl-2-benzoylanilines and corresponding imines and then evaluated for their central nervous system activities. Pharmacological data showed that some of these compounds have potent antidepressant properties, as assessed by their antagonism of tetrabenzine (TBZ) induced ptosis and their inhibition of [3H]norepinephrine uptake into rat brain synaptosomes, as well as their moderate antianxiety properties of preventing of pentylenetetrazol (PTZ) convulsion, suppressing conflict behavior, and displacing potential for [3H]diazepam binding. Introduction of a halogen substituent at position 7 of the 1,4-benzodiazepine ring lengthened the anti-PTZ effects, although the peak effect was slightly reduced and clearly enhanced the anti-PTZ and anticonflict properties. Introduction of Cl to the ortho position of the phenyl ring at position 5 greatly reduced the antidepressant properties. The secondary amine function of the azacyclic ring at position 1 was essential for the production of the antidepressant properties. Of these new series, 7-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1-(4-piperidinyl)-2H-1,4-benzodi azepin-2 -one has the potential to become a useful antidepressant drug with a moderate antianxiety property.

  DOI：

  10.1021/jm00383a003

文献信息

• 1,4-Benzodiazepine derivatives
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0111864A1

  公开（公告）日：1984-06-27

  1,4-Benzodiazepine derivatives of the formula: (in which R1 is pyrrolidinyl or piperidinyl each optionally substituted by C1-3 alkyl, phenyl-C1-3 alkyl, C1-5 alkanoyl, or C2-5 alkoxycarbonyl, R2 is hydrogen, hydroxy, or acetoxy, R3 is C1-3 alkyl, phenyl-C1-3 alkyl, or phenyl optionally substituted by one or two halogens, X is hydrogen, halogen, C1-3 alkyl, C1-3 alkoxy, nitro, trifluoromethyl, or di-C1-3 alkyl-amino, and n is 1 or 2) or pharmaceutically acceptable acid addition salts thereof, which are useful as a psychotropic agent such as antidepressant or anxiolytic agent can be prepared from several routes.

  式中的 1,4-苯并二氮杂卓衍生物： (其中 R1 为吡咯烷基或哌啶基，各自任选被 C1-3 烷基、苯基-C1-3 烷基、C1-5 烷酰基或 C2-5 烷氧羰基取代、 R2 是氢、羟基或乙酰氧基、 R3 是 C1-3 烷基、苯基-C1-3 烷基或任选被一个或两个卤素取代的苯基、 X 是氢、卤素、C1-3 烷基、C1-3 烷氧基、硝基、三氟甲基或二-C1-3 烷基氨基，以及 n 是 1 或 2） 或其药学上可接受的酸加成盐，可用作抗抑郁或抗焦虑等精神药物。
• SUGASAWA, TSUTOMU;ADACHI, MAKOTO;SASAKURA, KAZUYUKI;MATSUSHITA, AKIRA;EIG+, J. MED. CHEM., 1985, 28, N 6, 699-707
  作者：SUGASAWA, TSUTOMU、ADACHI, MAKOTO、SASAKURA, KAZUYUKI、MATSUSHITA, AKIRA、EIG+

  DOI：——

  日期：——
• US4560684A
  申请人：——

  公开号：US4560684A

  公开（公告）日：1985-12-24
• 1-Azacycloalkyl-1,4-benzodiazepin-2-ones with antianxiety-antidepressant actions
  作者：Tsutomu Sugasawa、Makoto Adachi、Kazuyuki Sasakura、Akira Matsushita、Masami Eigyo、Teruo Shiomi、Haruyuki Shintaku、Yukio Takahara、Shunji Murata

  DOI：10.1021/jm00383a003

  日期：1985.6

  A series of 1-azacycloalkyl-1,4-benzodiazepin-2-ones were synthesized from 1-azacycloalkyl-2-benzoylanilines and corresponding imines and then evaluated for their central nervous system activities. Pharmacological data showed that some of these compounds have potent antidepressant properties, as assessed by their antagonism of tetrabenzine (TBZ) induced ptosis and their inhibition of [3H]norepinephrine uptake into rat brain synaptosomes, as well as their moderate antianxiety properties of preventing of pentylenetetrazol (PTZ) convulsion, suppressing conflict behavior, and displacing potential for [3H]diazepam binding. Introduction of a halogen substituent at position 7 of the 1,4-benzodiazepine ring lengthened the anti-PTZ effects, although the peak effect was slightly reduced and clearly enhanced the anti-PTZ and anticonflict properties. Introduction of Cl to the ortho position of the phenyl ring at position 5 greatly reduced the antidepressant properties. The secondary amine function of the azacyclic ring at position 1 was essential for the production of the antidepressant properties. Of these new series, 7-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1-(4-piperidinyl)-2H-1,4-benzodi azepin-2 -one has the potential to become a useful antidepressant drug with a moderate antianxiety property.