(Gly)₄-OtBu | 125559-06-0

• 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: (Gly)₄-OtBu
• 英文别名: tert-butyl 2-(2-(2-(2-aminoacetamido)acetamido)acetamido)acetate；Tert-butyl 2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetate
• CAS: 125559-06-0
• 化学式: C₁₂H₂₂N₄O₅
• 分子量: 302.33
• InChiKey: QHZBTKSNNHLXEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  17-methyl-4,5α-epoxy-6-one-3-methoxy-8-[thioacetic acid]morphinan 、 (Gly)₄-OtBu 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成
  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

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• COMPOSITIONS AND METHODS OF TREATING OPIOID ADDICTION
  申请人：Minneapolis Medical Research Foundation

  公开号：US20140093525A1

  公开（公告）日：2014-04-03

  The present invention relates to conjugates and vaccine compositions for treatment of opioid addiction, and methods of use of these conjugates and compositions.

  本发明涉及用于治疗阿片类药物成瘾的结合物和疫苗组合物，以及这些结合物和组合物的使用方法。
• A Fentanyl Vaccine Alters Fentanyl Distribution and Protects against Fentanyl-Induced Effects in Mice and Rats
  作者：Michael D. Raleigh、Federico Baruffaldi、Samantha J. Peterson、Morgan Le Naour、Theresa M. Harmon、Jennifer R. Vigliaturo、Paul R. Pentel、Marco Pravetoni

  DOI：10.1124/jpet.118.253674

  日期：2019.2

  Fentanyl is an extremely potent synthetic opioid that has been increasingly used to adulterate heroin, cocaine, and counterfeit prescription pills, leading to an increase in opioid-induced fatal overdoses in the United States, Canada, and Europe. A vaccine targeting fentanyl could offer protection against the toxic effects of fentanyl in both recreational drug users and others in professions at risk

  芬太尼是一种极其有效的合成阿片类药物，越来越多地用于掺假海洛因、可卡因和假冒处方药，导致美国、加拿大和欧洲因阿片类药物导致致命过量服用的情况有所增加。针对芬太尼的疫苗可以为娱乐性吸毒者和其他有意外接触风险的职业人士提供针对芬太尼毒性作用的保护。本研究的重点是开发一种疫苗，该疫苗由与匙孔血蓝蛋白 (KLH) 载体蛋白或 GMP 级亚基 KLH (sKLH) 缀合的基于芬太尼的半抗原 (F) 组成。与对照组相比，用 F-KLH 免疫小鼠和大鼠可减少芬太尼诱导的热板镇痛作用，并且在大鼠中减少芬太尼向大脑的分布。 F-KLH 不会降低等镇痛剂量的海洛因或羟考酮对大鼠的镇痛作用。为了评估疫苗对芬太尼毒性的影响，用 F-sKLH 或未结合的 sKLH 免疫的大鼠暴露于增加皮下剂量的芬太尼。 F-sKLH 疫苗接种使芬太尼诱导的镇痛和呼吸抑制的剂量反应曲线向右移动。纳洛酮在两组中都逆转了芬太尼的作用，表
• [EN] FENTANYL HAPTEN, FENTANYL HAPTEN-CONJUGATES, AND METHODS FOR MAKING AND USING<br/>[FR] HAPTÈNE DE FENTANYL, CONJUGUÉS D'HAPTÈNE DE FENTANYL ET PROCÉDÉS DE FABRICATION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV MINNESOTA

  公开号：WO2021092446A1

  公开（公告）日：2021-05-14

  This disclosure describes a fentanyl hapten, a fentanyl hapten-carrier conjugate, methods of making the fentanyl hapten and the fentanyl hapten-carrier conjugate, and methods of using the fentanyl hapten and the fentanyl hapten-carrier conjugate. The fentanyl hapten-carrier conjugate may be used, for example, as a prophylactic vaccine to counteract toxicity from exposure to fentanyl and its analogues. In some embodiments, the fentanyl hapten-carrier conjugate or a composition including the fentanyl hapten-carrier conjugate may be used in an anti-opioid vaccine.

  本公开描述了一种芬太尼半抗原、一种芬太尼半抗原载体共轭物、制备芬太尼半抗原和芬太尼半抗原载体共轭物的方法，以及使用芬太尼半抗原和芬太尼半抗原载体共轭物的方法。例如，芬太尼半抗原载体共轭物可用作一种预防疫苗，用于对抗芬太尼及其类似物的毒性。在某些实施例中，芬太尼半抗原载体共轭物或包括芬太尼半抗原载体共轭物的组合物可用作一种抗阿片类药物的疫苗。
• WO2022/78524
  申请人：——

  公开号：——

  公开（公告）日：——