N-(3-(4aR,7S,7aR,12bS)-7,9-dihydroxy-4,4a,7,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl-3-(tritylthio)propanamide | 1313816-39-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(3-(4aR,7S,7aR,12bS)-7,9-dihydroxy-4,4a,7,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl-3-(tritylthio)propanamide
• 英文别名: N-[4-[(4R,4aR,7S,7aR,12bS)-7,9-dihydroxy-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-yl]butyl]-3-tritylsulfanylpropanamide
• CAS: 1313816-39-5
• 化学式: C₄₂H₄₄N₂O₄S
• 分子量: 672.888
• InChiKey: HWBBSNFXPJEIGY-UZFRCSGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-(4aR,7S,7aR,12bS)-7,9-dihydroxy-4,4a,7,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl-3-(tritylthio)propanamide 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-(3-(4aR,7S,7aR,12bS)-7,9-dihydroxy-4,4a,7,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl-3-mercaptopropanamide
  参考文献：
  名称：

  A Vaccine Strategy that Induces Protective Immunity against Heroin

  摘要：

  Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.

  DOI：

  10.1021/jm200461m
• 作为产物：
  描述：

  盐酸海洛因 在 1-氯乙基氯甲酸酯 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 溶剂黄146 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 8.75h， 生成 N-(3-(4aR,7S,7aR,12bS)-7,9-dihydroxy-4,4a,7,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl-3-(tritylthio)propanamide
  参考文献：
  名称：

  [EN] HEROIN HAPTENS, IMMUNOCONJUGATES AND RELATED USES
  [FR] HAPTÈNES D'HÉROÏNE, IMMUNOCONJUGUÉS ET UTILISATIONS ASSOCIÉES

  摘要：

  本发明提供了新型海洛因半抗原化合物和海洛因免疫结合物，可用于体内产生特异性结合海洛因及其精神活性代谢物的抗体。本发明还提供了使用包含海洛因免疫结合物的疫苗进行主动或被动免疫方案的方法。本发明的组合物和方法对于预防和治疗海洛因成瘾是有用的。

  公开号：

  WO2013095321A1

文献信息

• A Vaccine Strategy that Induces Protective Immunity against Heroin
  作者：G. Neil Stowe、Leandro F. Vendruscolo、Scott Edwards、Joel E. Schlosburg、Kaushik K. Misra、Gery Schulteis、Alexander V. Mayorov、Joseph S. Zakhari、George F. Koob、Kim D. Janda

  DOI：10.1021/jm200461m

  日期：2011.7.28

  Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.
• [EN] HEROIN HAPTENS, IMMUNOCONJUGATES AND RELATED USES<br/>[FR] HAPTÈNES D'HÉROÏNE, IMMUNOCONJUGUÉS ET UTILISATIONS ASSOCIÉES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2013095321A1

  公开（公告）日：2013-06-27

  The present invention provides novel heroin hapten compounds and heroin immunoconjugates which can be used for in vivo production of antibodies that specifically bind to heroin and its psychoactive metabolites. The invention also provides methods of using vaccines comprising the heroin immunoconjugates in active or passive immunization protocols. The compositions and methods of the invention are useful for prevention and treatment of heroin addiction.

  本发明提供了新型海洛因半抗原化合物和海洛因免疫结合物，可用于体内产生特异性结合海洛因及其精神活性代谢物的抗体。本发明还提供了使用包含海洛因免疫结合物的疫苗进行主动或被动免疫方案的方法。本发明的组合物和方法对于预防和治疗海洛因成瘾是有用的。