4-[[4-[[2-[2-[5-[[2-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]acetyl]amino]pentylamino]-2-oxoethoxy]acetyl]amino]-2,6-dimethylphenyl]-piperidin-4-ylidenemethyl]-N,N-diethylbenzamide | 1391034-94-8

• 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: 4-[[4-[[2-[2-[5-[[2-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]acetyl]amino]pentylamino]-2-oxoethoxy]acetyl]amino]-2,6-dimethylphenyl]-piperidin-4-ylidenemethyl]-N,N-diethylbenzamide
• CAS: 1391034-94-8
• 化学式: C₅₈H₇₇N₇O₁₀
• 分子量: 1032.29
• InChiKey: CNKGZZGPSMZTBR-MDADLRLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  75
• 可旋转键数：
  23
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  220
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  对甲基苯甲酸甲酯 在 盐酸 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 偶氮二异丁腈 、 溴 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 87.0h， 生成 4-[[4-[[2-[2-[5-[[2-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]acetyl]amino]pentylamino]-2-oxoethoxy]acetyl]amino]-2,6-dimethylphenyl]-piperidin-4-ylidenemethyl]-N,N-diethylbenzamide
  参考文献：
  名称：

  Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers

  摘要：

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

  DOI：

  10.1021/ml300083p

文献信息

• Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers
  作者：Jessica H. Harvey、Darcie H. Long、Pamela M. England、Jennifer L. Whistler

  DOI：10.1021/ml300083p

  日期：2012.8.9

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.