去甲羟考酮盐酸盐 | 52446-25-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 去甲羟考酮盐酸盐
• 英文名称: noroxycodone hydrochloride
• 英文别名: (4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-1,2,3,4,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one;hydrochloride
• CAS: 52446-25-0
• 化学式: C₁₇H₁₉NO₄*ClH
• 分子量: 337.803
• InChiKey: IGNAMRAQFUFUMH-KCTCKCTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.13
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  67.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  去甲羟考酮盐酸盐 在 氯化铵 、 锌 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 6,7-didehydro-4,14-dihydroxy-3-methoxy-6,7:2',3'-indolomorphinan
  参考文献：
  名称：

  δ Opioid Affinity and Selectivity of 4-Hydroxy-3-methoxyindolomorphinan Analogues Related to Naltrindole

  摘要：

  To investigate the effect of the introduction of a 4-phenolic substituent on the delta opioid affinity and selectivity of the indolomorphinans, a range of 4-phenolic analogues of naltrindole were prepared and evaluated in in vitro assays. Although the majority of the ligands displayed poor affinity for all three opioid receptors (mu, kappa, delta), 17-cyclopropylmethyl-6,7-didehydro-4-hydroxy-3-methoxy-6,7:2',3'-indolomorphinan (13) was an exception, displaying excellent delta binding selectivity (delta K-i = 7 nM, mu/delta = 1900, mu/kappa = 1130). GTP-gamma-S functional assays showed 13 to be a selective delta antagonist, albeit with lower potency than naltrindole. Although the reason for the unique profile of 13 could not be determined, these results validate our approach of introducing groups into the indolomorphinans that are known to reduce mu activity, to obtain increased delta selectivity.

  DOI：

  10.1021/jm9807003
• 作为产物：
  描述：

  蒂巴因 在 盐酸 、 甲酸 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 N,N,N,N-tetraethylammonium tetrafluoroborate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 5.0~100.0 ℃ 、101.33 kPa 条件下， 反应 12.12h， 生成 去甲羟考酮盐酸盐
  参考文献：
  名称：

  14-羟基吗啡烷的电化学 N-去甲基化：可持续获得阿片类拮抗剂。

  摘要：

  许多阿片拮抗剂制备过程中最具挑战性的步骤是14-羟基吗啡喃前体的选择性N-去甲基化。该过程使用化学计量数量的危险化学品（如溴化氰或氯甲酸酯）大规模进行。我们开发了一种温和的无试剂和无催化剂程序，用于基于叔胺阳极氧化的N-去甲基化步骤。随后的中间体可以很容易地以非常好的产率水解为目标去甲阿片类药物。

  DOI：

  10.1021/acs.orglett.0c02424

文献信息

• [EN] PROCESSES FOR PREPARING NOR-OPIOID COMPOUNDS AND OPIOID ANTAGONISTS BY ELECTROCHEMICAL N-DEMETHYLATION<br/>[FR] PROCÉDÉS DE PRÉPARATION DE COMPOSÉS OPIOÏDES NOR ET D'ANTAGONISTES OPIOÏDES PAR N-DÉMÉTHYLATION ÉLECTROCHIMIQUE
  申请人：RES CENTER PHARMACEUTICAL ENGINEERING GMBH

  公开号：WO2021249708A1

  公开（公告）日：2021-12-16

  The present invention relates to a process for preparing a nor-opioid compound wherein an opioid precursor compound is electrochemically N-demethylated. The present invention further relates to a process for preparing an opioid antagonist compound, wherein an opioid precursor compound is electrochemically N-demethylated and the thus obtained nor-opioid compound is alkylated again at its secondary amine functional group.

  本发明涉及一种制备诺阿片类化合物的方法，其中通过电化学方法对阿片类前体化合物进行N-去甲基化。本发明还涉及一种制备阿片类拮抗剂化合物的方法，其中通过电化学方法对阿片类前体化合物进行N-去甲基化，并且再次在其次胺官能团上进行烷基化得到的诺阿片类化合物。
• Syntheses of Potential Metabolites of a Potent .KAPPA.-Opioid Receptor Agonist, TRK-820
  作者：Kuniaki Kawamura、Hiromasa Horikiri、Jun Hayakawa、Chie Seki、Ken-ichi Yoshizawa、Hideo Umeuchi、Hiroshi Nagase

  DOI：10.1248/cpb.52.670

  日期：——

  Chemical syntheses of three kinds of potential metabolites of TRK-820, a potent κ-opioid receptor agonist, were described. One of the potential metabolites 2, 17-N-dealkylated TRK-820, was synthesized starting from noroxycodone through 8 steps in 21% total yield. Glucuronidation of intermediate 10 and compound 1, the free base of TRK-820, was carried out stereoselectively to give 3-O-β-D-glucuronides 15 and 16 in good yields, respectively. Syntheses of potential conjugated metabolites 3 and 4 were accomplished through 10 steps and 2 steps in 11% and 43% total yields, respectively. Among the potential metabolites of TRK-820, compounds 2 and 4 were identified as metabolites in human hepatocytes. The results of pharmacological studies of compounds 2, 3, and 4 are described.

  描述了三种潜在的TRK-820代谢物的化学合成，TRK-820是一种有效的κ-opioid受体激动剂。其中一种潜在代谢物2，17-N-去烷基TRK-820从noroxycodone出发通过8步合成，总产率为21%。对中间体10和化合物1（TRK-820的游离碱）进行立体选择性葡萄糖醛酸化，分别获得了良好产率的3-O-β-D-葡萄糖醛酸酯15和16。潜在的结合代谢物3和4通过10步和2步合成，总产率分别为11%和43%。在TRK-820的潜在代谢物中，化合物2和4被确定为人肝细胞中的代谢物。描述了化合物2、3和4的药理学研究结果。
• Organophotocatalytic N‐Demethylation of Oxycodone Using Molecular Oxygen
  作者：Yuesu Chen、Gabriel Glotz、David Cantillo、C. Oliver Kappe

  DOI：10.1002/chem.201905505

  日期：2020.3.2

  N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N-demethylation step using molecular oxygen as the terminal oxidant

  羟考酮的N-去甲基化是合成重要的阿片类拮抗剂（如纳洛酮）或镇痛药（如纳布啡）的关键步骤之一。该反应通常使用化学计量的有毒和腐蚀性试剂进行。在这里，我们提出了一种绿色且可扩展的有机光催化程序，该程序使用分子氧作为末端氧化剂和有机染料（孟加拉红）作为有效的光催化剂来完成N-脱甲基步骤。使用可见光辐照在连续流动条件下优化反应条件导致了高效，可靠和可扩展的工艺，在简单的后处理后，即可生产出高分离收率和纯度的去甲羟可待酮盐酸盐。
• Two-Step Iron(0)-Mediated N-Demethylation of <i>N</i>-Methyl Alkaloids
  作者：Gaik B. Kok、Cory C. Pye、Robert D. Singer、Peter J. Scammells

  DOI：10.1021/jo1008492

  日期：2010.7.16

  A mild and simple two-step Fe(0)-mediated N-demethylation of a number of tertiary N-methyl alkaloids is described. The tertiary N-methylamine is first oxidized to the corresponding N-oxide, which is isolated as the hydrochloride salt. Subsequent treatment of the N-oxide hydrochloride with iron powder readily provides the N-demethylated amine. Representative substrates include a number of opiate and tropane alkaloids. Key intermediates in the synthesis of semisynthetic 14-hydroxy pharmaceutical opiates such as oxycodone and oxymorphone are also readily N-demethylated using this method.
• [EN] CONJUGATES FOR ASSAYS FOR OXYCODONE AND OXYMORPHONE<br/>[FR] CONJUGUÉS UTILISABLES EN VUE DU DOSAGE DE L'OXYCODONE ET DE L'OXYMORPHONE
  申请人：SIEMENS HEALTHCARE DIAGNOSTICS INC

  公开号：WO2016100113A3

  公开（公告）日：2016-08-18