1-((-)-N-cyclobutylmethylmorphinan-3-yl) 10-(3,6-diol-7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)morphinan-3-yl)sebacoylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 1-((-)-N-cyclobutylmethylmorphinan-3-yl) 10-(3,6-diol-7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)morphinan-3-yl)sebacoylate
• 英文别名: MCL-196；10-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 1-O-[(1R,9R,10R)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] decanedioate
• 化学式: C₄₈H₆₂N₂O₆
• 分子量: 763.03
• InChiKey: VAFOYDSKVKJZEN-AQKJCXQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  56
• 可旋转键数：
  15
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  88.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  sebacic acid 10-((-)-N-cyclobutylmethylmorphinan-3-yl) ester 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-((-)-N-cyclobutylmethylmorphinan-3-yl) 10-(3,6-diol-7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)morphinan-3-yl)sebacoylate
  参考文献：
  名称：

  Synthesis and Preliminary In vitro Investigation of Bivalent Ligands Containing Homo- and Heterodimeric Pharmacophores at μ, δ, and κ Opioid Receptors

  摘要：

  A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [S-35]- GTP gamma S binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.

  DOI：

  10.1021/jm050577x

文献信息

• Synthesis and Preliminary In vitro Investigation of Bivalent Ligands Containing Homo- and Heterodimeric Pharmacophores at μ, δ, and κ Opioid Receptors
  作者：Xuemei Peng、Brian I. Knapp、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1021/jm050577x

  日期：2006.1.1

  A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [S-35]- GTP gamma S binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.