2-(2-(2-(((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate | 81941-17-5

• 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: 2-(2-(2-(((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate
• CAS: 81941-17-5
• 化学式: C₃₃H₄₄N₂O₈S
• 分子量: 628.787
• InChiKey: SBKNECWDWZKWBL-UWSOGJJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  44.0
• 可旋转键数：
  14.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  126.79
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  sodium methylate 、 2-(2-(2-(((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate 以 甲醇 为溶剂， 反应 3.0h， 以0.075 g的产率得到1-methoxy-8-naltrexamino-3,6-dioxaoctane
  参考文献：
  名称：

  Narcotic antagonistic potency of bivalent ligands which contain .beta.-naltrexamine. Evidence for simultaneous occupation of proximal recognition sites

  摘要：

  Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene units possessed 10-fold greater antagonistic potency than its monovalent analogue (4) in antagonizing the effects of ethylketazocine (EK) on the GPI, while no differential antagonism of morphine was observed among the compounds. In the MVD, 2 was not substantially more potent than 4 as an antagonist against [D-Ala2,D-Leu5]enkephalin (DADLE). The bivalent ligand 3, whose spanner contains six ethylene units, exhibited 15 times greater potency in antagonizing the agonist effects of DADLE on the MVD than its monovalent ligand 4. No marked increase in the ability of 3 to antagonize the effects of morphine or EK on the GPI was observed. The data indicate that mu, kappa, and delta opioid receptors exhibit different selectivity toward bivalent ligands whose spanner lengths differ. The enhanced potency associated with different receptor interactions is consistent with simultaneous occupation of proximal recognition sites. Whether such proximal recognition sites are identical or different remains to be clarified. The distance between proximal sites appears to depend on the opioid receptor subtype involved.

  DOI：

  10.1021/jm00349a016
• 作为产物：
  描述：

  (5alpha,6beta)-6-氨基-17-(环丙基甲基)-4,5-环氧-吗喃-3,14-二醇 、 三乙二醇二(对甲苯磺酸酯) 在 碳酸氢钠 作用下， 以 二乙二醇二甲醚 、 甲苯 为溶剂， 反应 5.0h， 以440 mg的产率得到2-(2-(2-(((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Investigation of the structural requirements for the .kappa.-selective opioid receptor antagonist 6.beta.,6.beta.'-[ethylenebis(oxyethyleneimino)]bis[17-(cyclopropylmethyl)-4,5.alpha.-epoxymorphinan-3,14-diol](TENA)

  摘要：

  In an effort to determine whether or not the basic nitrogens in the spacer of the bivalent ligand 6 beta,6 beta'-[ethylenebis(oxyethyleneimino)]bis[17-(cyclopropylmethyl)4,5 alpha-epoxymorphinan-3,14-diol] (TENA, 1) is responsible for its selective kappa opioid antagonist activity, we have synthesized monovalent analogues 2-4 that contain a C-6 side chain with basic nitrogens. Analogue 2 behaved as a potent opioid agonist in the guinea pig ileum preparation (GPI) and possessed no significant kappa opioid antagonist activity (IC50 ratio = 1) relative to TENA (IC50 ratio = 20). The agonist activity of 3 and 4 interfered with the opioid antagonist assay and therefore did not permit evaluation of antagonist activity in a concentration range where TENA is effective. Although the results obtained with 2 are consistent with the requirement of a second opiate pharmacophore (rather than a second basic nitrogen in the spacer) for the kappa antagonist activity of TENA, the potent agonism associated with these monomers do not allow a firm conclusion in this regard.

  DOI：

  10.1021/jm00155a048