methyl (Z)-[4,4-difluoro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetate | 183171-60-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: methyl (Z)-[4,4-difluoro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetate
• CAS: 183171-60-0
• 化学式: C₂₀H₁₆F₂N₂O₅
• 分子量: 402.354
• InChiKey: WJZXGCRTHWJNAK-VBKFSLOCSA-N

物化性质

• 沸点：
  558.3±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  89.75
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl (Z)-[4,4-difluoro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetate 在 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 5.0h， 以84%的产率得到methyl (Z)-[1-(4-aminobenzoyl)-4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetate
  参考文献：
  名称：

  Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as non-peptide antagonists of the arginine vasopressin V1A receptor

  摘要：

  To find potent and selective antagonists of the arginine vasopressin (AVP) V-1A receptor, optimization studies of compounds structurally related to (Z)-N-{4'-[(4,4-difluoro-5-carbamoylmethylidene-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbon-yl]phenyl}carboxamide were performed. The synthesis and phamacological properties of these compounds are described. We first investigated the effect of the carboxamide moiety, and found that a 2-methylfuran-3-carbonyl group at this position increased V-1A binding affinity and selectivity for the V-1A receptor versus the V-2 receptor. The amino group of the 5-carbamoylmethylidene moiety was also examined, and a 4-piperidinopiperidino group was found to be optimal at this position. The hemifumarate of compound 121 (YM218) was shown to exhibit potent binding affinity, V-1A receptor selectivity, and in vivo antagonist activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.035
• 作为产物：
  描述：

  methyl (2Z)-(4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate 、 4-硝基苯甲酰氯 以 二氯甲烷 为溶剂， 反应 12.0h， 以78%的产率得到methyl (Z)-[4,4-difluoro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetate
  参考文献：
  名称：

  Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as non-peptide antagonists of the arginine vasopressin V1A receptor

  摘要：

  To find potent and selective antagonists of the arginine vasopressin (AVP) V-1A receptor, optimization studies of compounds structurally related to (Z)-N-{4'-[(4,4-difluoro-5-carbamoylmethylidene-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbon-yl]phenyl}carboxamide were performed. The synthesis and phamacological properties of these compounds are described. We first investigated the effect of the carboxamide moiety, and found that a 2-methylfuran-3-carbonyl group at this position increased V-1A binding affinity and selectivity for the V-1A receptor versus the V-2 receptor. The amino group of the 5-carbamoylmethylidene moiety was also examined, and a 4-piperidinopiperidino group was found to be optimal at this position. The hemifumarate of compound 121 (YM218) was shown to exhibit potent binding affinity, V-1A receptor selectivity, and in vivo antagonist activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.035