17-methyl-4,5α-epoxy-6-one-3-methoxy-8-[thio-N-(glycylglycylglycylglycine)acetamido]morphinan | 1418280-97-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 17-methyl-4,5α-epoxy-6-one-3-methoxy-8-[thio-N-(glycylglycylglycylglycine)acetamido]morphinan
• 英文别名: 8-thioacetic acid hydrocodone；2-[[2-[[2-[[2-[[2-[[(4R,4aR,7aR,12bS)-9-methoxy-3-methyl-7-oxo-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-5-yl]sulfanyl]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]acetic acid
• CAS: 1418280-97-3
• 化学式: C₂₈H₃₅N₅O₉S
• 分子量: 617.68
• InChiKey: HKIQECMIUZJMPA-POOBPXBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  218
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  可待因酮 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 17-methyl-4,5α-epoxy-6-one-3-methoxy-8-[thio-N-(glycylglycylglycylglycine)acetamido]morphinan
  参考文献：
  名称：

  Reduced Antinociception of Opioids in Rats and Mice by Vaccination with Immunogens Containing Oxycodone and Hydrocodone Haptens

  摘要：

  Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (60XY(Gly)(4)OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (60XY(Gly)(4)-KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 60XY(Gly)(4)-KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 60XY(Gly)(4)-KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 60XY(Gly)(4)-KLH vaccine may be used for treatment of prescription opioid abuse.

  DOI：

  10.1021/jm3013745

文献信息

• Reduced Antinociception of Opioids in Rats and Mice by Vaccination with Immunogens Containing Oxycodone and Hydrocodone Haptens
  作者：Marco Pravetoni、Morgan Le Naour、Ashli M. Tucker、Theresa M. Harmon、Tara M. Hawley、Philip S. Portoghese、Paul R. Pentel

  DOI：10.1021/jm3013745

  日期：2013.2.14

  Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (60XY(Gly)(4)OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (60XY(Gly)(4)-KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 60XY(Gly)(4)-KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 60XY(Gly)(4)-KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 60XY(Gly)(4)-KLH vaccine may be used for treatment of prescription opioid abuse.