8-(4-{[(2,3-dihydronaphtho[1,2-b]dioxin-2-yl)methyl]amino}butyl)-8-azaspiro[4.5]decane-7,9-dione | 113777-34-7

• 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: 8-(4-{[(2,3-dihydronaphtho[1,2-b]dioxin-2-yl)methyl]amino}butyl)-8-azaspiro[4.5]decane-7,9-dione
• 英文别名: 8-[4-(2,3-Dihydrobenzo[h][1,4]benzodioxin-2-ylmethylamino)butyl]-8-azaspiro[4.5]decane-7,9-dione
• CAS: 113777-34-7
• 化学式: C₂₆H₃₂N₂O₄
• 分子量: 436.551
• InChiKey: VFKQPDBDZNBCKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 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-(aminomethyl)-1,4-naphtho<1,2-b>dioxane 、 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， 以45.9%的产率得到8-(4-{[(2,3-dihydronaphtho[1,2-b]dioxin-2-yl)methyl]amino}butyl)-8-azaspiro[4.5]decane-7,9-dione
  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

• Glutarimide antianxiety and antihypertensive agents
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0170213A1

  公开（公告）日：1986-02-05

  Glutarimide derivatives of the formula which are useful antihypertensive and antianxiety agents wherein R1 and R2 each independently represent hydrogen, a 1 to 4 carbon alkyl, a 1 to 4 carbon alkoxy, halogen, nitro, hydroxy, S03H, S02NH2, and when R1 and R2 are taken together, form a fused phenyl group at the 1,2- or 3,4- positions, with the proviso that when R1 and R2 are identical they each represent a hydrogen, a 1 to 4 carbon alkyl, a 1 to 4 carbon alkoxy, hydroxy or a halogen group; A and B independently represent an oxo, a thio or an imino group having the formula -N(R6)- wherein the R6 group is hydrogen or a 1 to 4 carbon alkyl group; R3 is a hydrogen, a 1 to 4 carbon alkyl or hydroxyethyl group; n is an integer of from 2 to 5; and R4 and R6 represent methyl groups or when taken together form a cyclopentane or cyclohexane ring; its enantiomers; and the pharmaceutically acceptable acid addition salts thereof.

  可用于降压和抗焦虑的式中戊二酰亚胺衍生物 其中 R1 和 R2 各自独立地代表氢、1-4 碳烷基、1-4 碳烷氧基、卤素、硝基、羟基、S03H、S02NH2，当 R1 和 R2 合在一起时，在 1,2- 或 3,4- 位上形成一个融合苯基，但当 R1 和 R2 相同时，它们各自代表氢、1-4 碳烷基、1-4 碳烷氧基、羟基或卤素基团；A 和 B 独立地代表一个氧代、硫代或亚氨基基团，其式为 -N(R6)-，其中 R6 基团是氢或 1 至 4 碳烷基；R3 是氢、1 至 4 碳烷基或羟乙基；n 是 2 至 5 的整数；R4 和 R6 代表甲基或当它们结合在一起时形成环戊烷或环己烷环；其对映体；及其药学上可接受的酸加成盐。
• USE OF CERTAIN GLUTARIMIDE DERIVATIVES IN THE TREATMENT OF DEPRESSION AND MANIA
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0564520A1

  公开（公告）日：1993-10-13
• [EN] USE OF CERTAIN GLUTARIMIDE DERIVATIVES IN THE TREATMENT OF DEPRESSION AND MANIA
  申请人：——

  公开号：WO1992011011A1

  公开（公告）日：1992-07-09

  [EN] This invention relates to the manufacture of certain glutarimide derivatives for their use as medicaments in the treatment of depression and mania.
  [FR] L'invention se rapporte à la fabrication de certains dérivés de glutarimide en vue de leur utilisation comme médicaments dans le traitement de la dépression et des états maniaques.
• 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.