20-Naphthalen-2-yl-16,19-diazapentacyclo[12.6.0.02,7.08,13.015,19]icosa-1(14),2,4,6,8,10,12,15-octaen-20-ol

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 20-Naphthalen-2-yl-16,19-diazapentacyclo[12.6.0.02,7.08,13.015,19]icosa-1(14),2,4,6,8,10,12,15-octaen-20-ol
• 化学式: C₂₈H₂₀N₂O
• 分子量: 400.48
• InChiKey: VEOHXIUSARYQDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  9-腈菲 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 乙二醇 为溶剂， 反应 48.25h， 生成 20-Naphthalen-2-yl-16,19-diazapentacyclo[12.6.0.02,7.08,13.015,19]icosa-1(14),2,4,6,8,10,12,15-octaen-20-ol
  参考文献：
  名称：

  Benzo- and Cyclohexanomazindol Analogues as Potential Inhibitors of the Cocaine Binding Site at the Dopamine Transporter

  摘要：

  A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives with a benzo or cyclohexano ring fused At various sites were prepared as part of an SAR study to determine the effect of increased aliphatic and aromatic lipophilicity on selected in vitro assays used to identify potential cocaine-like and cocaine antagonism activity. Very good (IC50 = 2-3 nM) inhibition of [H-3] WIN 35,428 and [I-125] RTI-55 binding on rat or guinea pig striatal membranes and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new compounds were weaker inhibitors of [H-3] DA uptake in HEK-hDAT cells than 1 and 2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was found when compared to 2. Compounds 25 and 28 showed a considerable increase versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs 0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).

  DOI：

  10.1021/jm010301z

文献信息

• Benzo- and Cyclohexanomazindol Analogues as Potential Inhibitors of the Cocaine Binding Site at the Dopamine Transporter
  作者：William J. Houlihan、Umer F. Ahmad、Judith Koletar、Lawrence Kelly、Leonard Brand、Theresa A. Kopajtic

  DOI：10.1021/jm010301z

  日期：2002.9.1

  A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives with a benzo or cyclohexano ring fused At various sites were prepared as part of an SAR study to determine the effect of increased aliphatic and aromatic lipophilicity on selected in vitro assays used to identify potential cocaine-like and cocaine antagonism activity. Very good (IC50 = 2-3 nM) inhibition of [H-3] WIN 35,428 and [I-125] RTI-55 binding on rat or guinea pig striatal membranes and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new compounds were weaker inhibitors of [H-3] DA uptake in HEK-hDAT cells than 1 and 2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was found when compared to 2. Compounds 25 and 28 showed a considerable increase versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs 0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).