盐酸海洛因 | 1502-95-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: 盐酸海洛因
• 英文名称: heroin hydrochloride
• 英文别名: diacetylmorphine hydrochloride；Acetomorphin hydrochloride；diamorphine hydrochloride；heroin；3,6-diacetylmorphine hydrochloride；BAN hydrochloride；[(4R,4aR,7S,7aR,12bS)-9-acetyloxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] acetate;hydrochloride
• CAS: 1502-95-0
• 化学式: C₂₁H₂₃NO₅*ClH
• 分子量: 405.878
• InChiKey: FZJYQGFGNHGSFX-PVQKIFDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.42
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 10.0h， 生成 (4aR,7S,7aR,12bS)-3-(3-(3-mercaptopropanamido)butyl)-2,3,4,4a,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diyl diacetate
  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

• Diamorphine stability in aqueous solution for subcutaneous infusion
  作者：O A Omar、P J Hoskin、A Johnston、G W Hanks、P Turner

  DOI：10.1111/j.2042-7158.1989.tb06452.x

  日期：2011.4.12

  The influence of temperature and concentration on diamorphine stability during storage over 8 weeks has been investigated. Ampoules containing diamorphine hydrochloride in concentrations from 0·98–250 mg mL−1 have been stored at −20, 4, 21 and 37°C for 8 weeks. Their content of diamorphine, 6-monoacetylmorphine and morphine, on measurement by high performance liquid chromatography after 1, 2, 4, 6 and 8 weeks storage changed to slow degradation of diamorphine at all concentrations at temperatures of 4°C and above. This was accompanied by a corresponding increase in 6-monoacetylmorphine and morphine. There was an associated fall in pH and development of a strong odour characteristic of acetic acid. Precipitation and a white turbidity seen in solutions of 15·6 mg mL and above, appeared after 2 weeks incubation.

  温度和浓度对地西泮在8周存储期间稳定性的影响已经被调查。含有地西泮盐酸盐，浓度从0.98-250毫克/毫升的安瓿在-20、4、21和37摄氏度下存储了8周。经过1、2、4、6和8周存储后，通过高效液相色谱测量，地西泮、6-单乙酰吗啡和吗啡的含量在4摄氏度及以上的所有浓度下发生缓慢降解。这伴随着6-单乙酰吗啡和吗啡的相应增加。伴随着pH值下降和产生乙酸特征性的强烈气味。在15.6毫克/毫升及以上的溶液中出现的沉淀和白色浑浊物，在孵育2周后出现。
• A chemically contiguous hapten approach for a heroin–fentanyl vaccine
  作者：Yoshihiro Natori、Candy S Hwang、Lucy Lin、Lauren C Smith、Bin Zhou、Kim D Janda

  DOI：10.3762/bjoc.15.100

  日期：——

  Background: Increased death due to the opioid epidemic in the United States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin.

  Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine.

  Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin–fentanyl vaccine. Importantly, this is the first report of such a strategy in the opioid–drug–vaccine field.

  背景：美国阿片类药物危机导致死亡人数增加，迫使开发新策略来治疗成瘾问题。单克隆抗体和抗药疫苗提供了一种既有助于成瘾管理又减少过量风险的工具。通过连续偶联或混合制备的双药物疫苗存在一定缺陷。本研究探讨了一种对抗含芬太尼的海洛因危险的方法，即使用一个具有既有芬太尼又有海洛因结构域的半抗原。 结果：我们评估了一系列由化学上相邻的半抗原组成的九种疫苗，其中包含海洛因和芬太尼样结构域。通过表面等离子共振和酶联免疫吸附分析结果，发现了基于表位大小和连接位置的海洛因和芬太尼抗体亲和力和滴度的趋势。在镇痛研究中，表现最佳的疫苗对海洛因提供了与我们基准海洛因疫苗相当的保护，但与我们的芬太尼疫苗相比，对芬太尼的保护效果有所减弱。 结论：经过对这一策略的深入研究，我们确定了开发化学上相邻的海洛因-芬太尼疫苗的关键考虑因素。重要的是，这是阿片类药物-疫苗领域首次报道这种策略。
• [EN] AN IMPROVED HEROIN VACCINE<br/>[FR] VACCIN CONTRE L'HÉROÏNE AMÉLIORÉ
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2019094528A1

  公开（公告）日：2019-05-16

  An improved heroin conjugate vaccine is detailed; to accomplish this task the systematic exploration of twenty vaccine formulations with varying combinations of carrier proteins and adjuvants were undertaken. In regard to adjuvants, a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum were explored. The vaccine formulations containing TLR3 or TLR9 agonist alone-elicited strong anti-heroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and 9 adjuvants did not result in improved efficacy. Investigation of stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored over 30 days. Furthermore, mice immunized with the TLR9 + alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the lethal effects of heroin, even following long-term storage at room temperature.

  详细介绍了一种改进的海洛因结合疫苗；为了完成这项任务，进行了对二十种疫苗配方的系统探索，这些配方采用了不同载体蛋白和佐剂的组合。在佐剂方面，研究了存在于氢氧化铝中的Toll样受体9（TLR9）激动剂和Toll样受体3（TLR3）激动剂。含有单独的TLR3或TLR9激动剂的疫苗配方在与氢氧化铝配方时引发了强烈的抗海洛因抗体滴度和阻断海洛因诱导的止痛作用；然而，TLR3和9激动剂的组合并没有导致疫效的改善。对两种主要配方的稳定性进行的调查显示，存放超过30天时，TLR9配方而不是TLR3配方是稳定的。此外，接种了TLR9 + 氢氧化铝海洛因疫苗的小鼠对致命海洛因剂量获得了显著的保护，表明这种疫苗配方适用于减轻海洛因的致命影响，即使在室温下长期存放后也是如此。
• Benzoamide piperidine containing compounds and related compounds
  申请人：——

  公开号：US20030087925A1

  公开（公告）日：2003-05-08

  The present invention relates to certain benzoamide piperidine containing compounds and related compounds that exhibit activity as NK-1 receptor antagonists, (e.g., substance P receptor antagonists), to pharmaceutical compositions containing them, and to their use in the treatment and prevention of central nervous system disorders, inflammatory disorders, cardiovascular disorders, ophthalmic disorders, gastrointestinal disorders, disorders caused by helicobacter pylori, disorders of the immune system, urinary incontinence, pain, migraine, emesis, angiogenesis and other disorders.

  本发明涉及某些含有苯甲酰胺哌啶类化合物和相关化合物，这些化合物表现出作为NK-1受体拮抗剂（例如，物质P受体拮抗剂）的活性，以及含有它们的药物组合物，以及它们在治疗和预防中枢神经系统疾病、炎症性疾病、心血管疾病、眼科疾病、消化系统疾病、幽门螺杆菌引起的疾病、免疫系统疾病、尿失禁、疼痛、偏头痛、呕吐、血管生成和其他疾病的治疗中的用途。
• PIPERIDINE DERIVATIVES AND THEIR USE AS TACHYKININ ANTAGONISTS
  申请人：——

  公开号：US20020052504A1

  公开（公告）日：2002-05-02

  Substituted piperidine derivatives of structural formula (I) wherein R1 represents a hydrogen atom or a methyl or trifluoromethyl group; R2 represents a hydrogen or halogen atom, and R3 represents a hydrogen or halogen atom, and pharmaceutically acceptable salts thereof are tachykinin receptor antagonists of use, for example, in the treatment or prevention of pain, inflammation, migraine, emesis, postherpetic neuralgia, depression and anxiety.

  结构式（I）中的取代哌啶衍生物，其中R1代表氢原子或甲基或三氟甲基基团；R2代表氢或卤原子，R3代表氢或卤原子，以及其药用可接受的盐是可用的催吐肽受体拮抗剂，例如，用于治疗或预防疼痛、炎症、偏头痛、呕吐、带状疱疹后神经痛、抑郁症和焦虑症。