| 80805-61-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 80805-61-4
• 化学式: C₁₆H₁₃ClN₂O₄
• 分子量: 332.743
• InChiKey: YXVBNCCPYXBFJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.76
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  81.8
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 硼烷四氢呋喃络合物 作用下， 生成 N-[1-(2-Chloro-phenyl)-2-(2-nitro-phenyl)-ethyl]-formamide
  参考文献：
  名称：

  (.+-.)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear substituted analogs of (.+-.)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (.+-.)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents

  摘要：

  Antidepressant-like activity, as evidenced by marked inhibition of tetrabenazine-induced ptosis, was previously reported for (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepine derivatives. Since optimal antitetrabenazine activity was associated with (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (9k, HRP 543) and the 2-ethyl-3-methyl analogue (10k), the synthesis and evaluation of nuclear-substituted derivatives of these two compounds was also investigated. The initial synthesis involved Friedel-Crafts acylation of substituted benzenes with 2-nitrophenylacetyl chloride to afford 1-aryl-2-(2-nitrophenyl)ethanones 2, which were converted in five steps to (+/-)-alpha-aryl-N-methyl-2-nitrobenzeneethanamines 7. Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis. Reductive amination of 2 with methylamine and sodium cyanoborohydride afforded 7 directly and significantly reduced the number of synthetic steps. Reduction of 7a-j to diamines 8a-j and cyclization with appropriate ortho esters gave nuclear-substituted analogues of 9k and 10k. Marked antitetrabenazine activity was associated with many of these compounds. Significant enhancement of activity with respect to the unsubstituted analogues 9k and 10k was not observed, with the exception of 9c which appeared to be slightly more potent than 9k.

  DOI：

  10.1021/jm00346a004
• 作为产物：
  描述：

  (Z)-1-(2-Chloro-phenyl)-3-dimethylamino-2-(2-nitro-phenyl)-propenone 在 盐酸羟胺 、 水 、 sodium acetate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  (.+-.)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear substituted analogs of (.+-.)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (.+-.)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents

  摘要：

  Antidepressant-like activity, as evidenced by marked inhibition of tetrabenazine-induced ptosis, was previously reported for (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepine derivatives. Since optimal antitetrabenazine activity was associated with (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (9k, HRP 543) and the 2-ethyl-3-methyl analogue (10k), the synthesis and evaluation of nuclear-substituted derivatives of these two compounds was also investigated. The initial synthesis involved Friedel-Crafts acylation of substituted benzenes with 2-nitrophenylacetyl chloride to afford 1-aryl-2-(2-nitrophenyl)ethanones 2, which were converted in five steps to (+/-)-alpha-aryl-N-methyl-2-nitrobenzeneethanamines 7. Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis. Reductive amination of 2 with methylamine and sodium cyanoborohydride afforded 7 directly and significantly reduced the number of synthetic steps. Reduction of 7a-j to diamines 8a-j and cyclization with appropriate ortho esters gave nuclear-substituted analogues of 9k and 10k. Marked antitetrabenazine activity was associated with many of these compounds. Significant enhancement of activity with respect to the unsubstituted analogues 9k and 10k was not observed, with the exception of 9c which appeared to be slightly more potent than 9k.

  DOI：

  10.1021/jm00346a004