β-funaltrexamine hydrochloride | 72786-10-8

• 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: β-funaltrexamine hydrochloride
• 英文别名: β-funaltrexamine；β-FNA hydrochloride；beta-Funaltrexamine hydrochloride；methyl (E)-4-[[(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]-4-oxobut-2-enoate;hydrochloride
• CAS: 72786-10-8
• 化学式: C₂₅H₃₀N₂O₆*ClH
• 分子量: 490.984
• InChiKey: BIPHUOBUKMPSQR-NQGXHZAGSA-N

物化性质

• 溶解度：
  H2O：7.5 mg/mL水溶液应及时使用

计算性质

• 辛醇/水分配系数(LogP)：
  1.59
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  β-funaltrexamine hydrochloride 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以71%的产率得到17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-6β-<(3-methoxycarbonyl)propionamido>morphinan hydrochloride
  参考文献：
  名称：

  具有非平衡阿片样激动剂和拮抗剂活性的纳曲酮衍生的亲和标签的设计和合成。在不同组织中存在不同mu受体亚型的证据。

  摘要：

  合成了一系列β-富纳曲胺（2，β-FNA）类似物（3-14），它们包含在鸦片剂的6β-位连接的各种亲电基团。这些配体的阿片样物质激动剂和拮抗剂活性在豚鼠回肠（GPI）和小鼠输精管（MVD）体外测定中进行了评估。几种化合物的行为类似于β-FNA，因为它们在κ阿片受体上表现出可逆的激动剂活性，而在μ阿片受体上表现出不可逆的拮抗剂活性。一系列相关迈克尔受体的不可逆拮抗作用的等级顺序与它们的内在化学反应性并不平行，这证实了共价结合的程度部分取决于亲电子中心相对于受体亲核试剂的空间位置（二次识别）。马来酰亚胺基乙酰胺8的行为与β-FNA非常不同，相对于GPI中的mu阻滞，它在MVD中表现出更大的不可逆mu拮抗作用。这表明在两个组织中存在不同比例的mu受体亚型。测试的几种药物，包括一些非反应性对照化合物，在GPI中表现出不同寻常的持久性Kappa激动剂活性。该活性通过添加纳洛酮而逆转，在洗涤时再次出现

  DOI：

  10.1021/jm00376a018

文献信息

• Possible contribution of a glutathione conjugate to the long-duration action of .beta.-funaltrexamine
  作者：D. L. Larson、M. Hua、A. E. Takemori、P. S. Portoghese

  DOI：10.1021/jm00075a023

  日期：1993.11

  The fumaramate derivative of naltrexone, beta-funaltrexamine (beta-FNA), is a highly selective long-lasting mu opioid receptor antagonist that is active both in vitro and in vivo, presumably as a result of covalent binding to au receptor-based sulfhydryl group. Glutathione, which occurs in significant levels in brain and liver, was found to undergo a Michael-type reaction with beta-FNA in the test tube to give a stable conjugate 3 which occurred as an isomeric mixture. When tested in the GPI and MVD smooth muscle preparations, 3 was found to possess one-tenth the agonist activity of beta-FNA is both tissues, but showed no irreversible antagonist activity. The same result was found for the cysteine conjugate 4, except for some irreversible antagonism in the MVD. Both conjugates antagonize the antinociceptive effect of morphine in the mouse radiant heat tail-flick assay on icv administration. This antagonism persisted and actually increased over 24 h and generally paralleled the duration profile of beta-FNA. On sc administration, beta-FNA and 3 showed similar duration of antagonistic effect, while 4 exhibited only marginal activity at the early time interval. When the compounds are compared by the dose to produce equivalent antagonism, beta-FNA and 3 appeared equally effective and accessible by either route, whereas 4 showed a large difference between the two routes. It is possible that the ultra-long antagonism of the conjugates may result from their enzymatic conversion to beta-FNA in the central nervous system in view of the fact that conjugate 5, which cannot be converted to beta-FNA, did not produce antagonism of long duration in vivo. Alternatively, the protracted antagonism could arise from sequestration of 3 and 4 in tissue compartments that interface with mu opioid receptors.
• Design and synthesis of naltrexone-derived affinity labels with nonequilibrium opioid agonist and antagonist activities. Evidence for the existence of different .mu. receptor subtypes in different tissues
  作者：L. M. Sayre、D. L. Larson、A. E. Takemori、P. S. Portoghese

  DOI：10.1021/jm00376a018

  日期：1984.10

  of the opiate. The opioid agonist and antagonist activities of these ligands were evaluated in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro assays. Several of the compounds behaved like beta-FNA in that they exhibited reversible agonist activity at kappa opioid receptors and irreversible antagonist activity at mu opioid receptors. The rank order of irreversible antagonism for a series

  合成了一系列β-富纳曲胺（2，β-FNA）类似物（3-14），它们包含在鸦片剂的6β-位连接的各种亲电基团。这些配体的阿片样物质激动剂和拮抗剂活性在豚鼠回肠（GPI）和小鼠输精管（MVD）体外测定中进行了评估。几种化合物的行为类似于β-FNA，因为它们在κ阿片受体上表现出可逆的激动剂活性，而在μ阿片受体上表现出不可逆的拮抗剂活性。一系列相关迈克尔受体的不可逆拮抗作用的等级顺序与它们的内在化学反应性并不平行，这证实了共价结合的程度部分取决于亲电子中心相对于受体亲核试剂的空间位置（二次识别）。马来酰亚胺基乙酰胺8的行为与β-FNA非常不同，相对于GPI中的mu阻滞，它在MVD中表现出更大的不可逆mu拮抗作用。这表明在两个组织中存在不同比例的mu受体亚型。测试的几种药物，包括一些非反应性对照化合物，在GPI中表现出不同寻常的持久性Kappa激动剂活性。该活性通过添加纳洛酮而逆转，在洗涤时再次出现