(-)-MDL 72832 | 102908-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: (-)-MDL 72832
• 英文别名: Tocris-0412；8-[4-[[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methylamino]butyl]-8-azaspiro[4.5]decane-7,9-dione
• CAS: 102908-55-4
• 化学式: C₂₂H₃₀N₂O₄
• 分子量: 386.491
• InChiKey: HCVRCHQFYYZPHT-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二恶-2-甲胺 、 N-<4-(tosyloxy)butyl>-3,3-tetramethyleneglutarimide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (+)-MDL 72832 、 (-)-MDL 72832
  参考文献：
  名称：

  Graphics computer-aided receptor mapping as a predictive tool for drug design: development of potent, selective, and stereospecific ligands for the 5-HT1A receptor

  摘要：

  A conformational study of four 5-HT1A (serotonin) receptor ligands ((R-(-)-methiothepin, spiperone, (S)-(-)-propranolol, and buspirone) led to the definition of a pharmacophore and a three-dimensional map of the 5-HT1A antagonist recognition site. These models were used to design new compounds and successfully predict their potency, stereospecificity, and selectivity. For example, 8-[4-[(1,4-benzodioxan-2-ylmethyl)amino] butyl]-8-azaspiro[4.5]decane-7,9-dione (1, MDL 72832) has nanomolar affinity (pIC50 = 9.14) for the 5-HT1A binding site in rat frontal cortex. As predicted, the S-(-) enantiomer of 1 was more active than its R-(+) enantiomer (pIC50 = 9.21 and 7.66, respectively) and a naphthalene analogue of 1 displayed the expected improved selectivity.

  DOI：

  10.1021/jm00401a007

文献信息

• Graphics computer-aided receptor mapping as a predictive tool for drug design: development of potent, selective, and stereospecific ligands for the 5-HT1A receptor
  作者：Marcel F. Hibert、Maurice W. Gittos、Derek N. Middlemiss、Anis K. Mir、John R. Fozard

  DOI：10.1021/jm00401a007

  日期：1988.6

  A conformational study of four 5-HT1A (serotonin) receptor ligands ((R-(-)-methiothepin, spiperone, (S)-(-)-propranolol, and buspirone) led to the definition of a pharmacophore and a three-dimensional map of the 5-HT1A antagonist recognition site. These models were used to design new compounds and successfully predict their potency, stereospecificity, and selectivity. For example, 8-[4-[(1,4-benzodioxan-2-ylmethyl)amino] butyl]-8-azaspiro[4.5]decane-7,9-dione (1, MDL 72832) has nanomolar affinity (pIC50 = 9.14) for the 5-HT1A binding site in rat frontal cortex. As predicted, the S-(-) enantiomer of 1 was more active than its R-(+) enantiomer (pIC50 = 9.21 and 7.66, respectively) and a naphthalene analogue of 1 displayed the expected improved selectivity.