纳美酮 | 16676-26-9

• 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: 纳美酮
• 英文名称: nalmexone
• 英文别名: (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-(3-methylbut-2-enyl)-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 16676-26-9
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: OHKCLOQPSLQCQR-MBPVOVBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  14-羟基二氢降吗啡酮盐酸盐 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 纳美酮
  参考文献：
  名称：

  Opioids and efflux transporters. Part 4: Influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues

  摘要：

  The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demonstrated to be up-regulated in rats tolerant to morphine and oxycodone. We have previously examined the influence of hydrogen-bonding oxo-substitutents on the P-gp-mediated efflux of 4,5-epoxymorphinan analgesics, as well as that of N-substituted analogues of meperidine. Structure activity relationships (SAR) governing N-substituent effects on opioid efficacy is well-established, however the influence of such structural modifications on P-gp-mediated efflux is unknown. Here, we present SAR describing P-gp recognition of a short series of N-modified 4,5-epoxymorphinans. Oxymorphone, naloxone, naltrexone, and nalmexone all failed to demonstrate P-gp substrate activity, indicating these opioid scaffolds contain structural features that preclude recognition by the transporter. These results are examined using mathematical molecular modeling and discussed in comparison to other opioid scaffolds bearing similar N-substituents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.033

文献信息

• [EN] CARBONATE PRODRUGS AND METHODS OF USING THE SAME<br/>[FR] PROMÉDICAMENTS CARBONATÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：NEUROGESX INC

  公开号：WO2009143297A1

  公开（公告）日：2009-11-26

  The present invention provides carbonate prodrugs which comprise a carbonic phosphoric anhydride prodrug moiety attached to the hydroxyl or carboxyl group of a parent drug moiety. The prodrugs may provide improved physicochemical properties over the parent drug. Also provided are methods of treating a disease or condition that is responsive to the parent drug using the carbonate prodrugs, as well as kits and unit dosages.

  本发明提供了碳酸盐前药，其包括连接到母药基团的羟基或羧基上的碳酸磷酸酐前药基团。这些前药可能比母药具有改进的物理化学性质。还提供了使用碳酸盐前药治疗对母药具有响应的疾病或症状的方法，以及配套工具和单剂量。
• [EN] NOVEL OPIOID COMPOUNDS AND USES THEREOF<br/>[FR] NOUVEAUX COMPOSÉS OPIOÏDES ET LEURS UTILISATIONS
  申请人：RHODES TECH

  公开号：WO2019165298A1

  公开（公告）日：2019-08-29

  This invention relates to novel opioid derivatives of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R3, R4 and Z are as defined herein in the disclosure. The invention also relates to the use of such compounds for the treatment or prevention of, for example, pain.

  这项发明涉及公式I的新型阿片类衍生物：或其药用可接受的盐或溶剂，其中R1、R3、R4和Z如本公开说明中所定义。该发明还涉及利用这类化合物治疗或预防疼痛等疾病的用途。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF PAIN AND DEPENDANCE DISORDERS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET DE TROUBLES DE LA DÉPENDANCE
  申请人：RIPPLE THERAPEUTICS CORP

  公开号：WO2021024039A1

  公开（公告）日：2021-02-11

  Provided herein are (e.g., controlled release) compositions for the treatment of acute or chronic diseases or disorders. Described herein are processable opioid conjugates. Also described herein are compositions and methods for the treatment of central nervous system (CNS) diseases or disorders including chronic pain (e.g., cancer pain), acute pain, opioid addiction, alcohol addiction, alcohol dependence, opioid-induced constipation, and narcotic depression. Said compositions and methods comprise opioid agonists and/or opioid antagonists, which demonstrate CNS activity and/or other desirable activities. Injection of said compositions subcutaneously or intraspinally provides therapeutic benefit to individuals suffering from CNS diseases or disorders

  本文提供了用于治疗急性或慢性疾病或障碍的（例如，控释）组合物。本文描述了可加工的阿片类结合物。本文还描述了用于治疗中枢神经系统（CNS）疾病或障碍的组合物和方法，包括慢性疼痛（例如，癌症疼痛）、急性疼痛、阿片类成瘾、酒精成瘾、酒精依赖、阿片类引起的便秘和麻醉性抑郁症。所述组合物和方法包括表现出CNS活性和/或其他理想活性的阿片类激动剂和/或阿片类拮抗剂。将所述组合物皮下或脊髓内注射可为患有中枢神经系统疾病或障碍的个体提供治疗益处。
• [EN] QUATERNARY OPIOID CARBOXAMIDES<br/>[FR] CARBOXAMIDES OPIOÏDES QUATERNAIRES
  申请人：RENSSELAER POLYTECH INST

  公开号：WO2009023567A1

  公开（公告）日：2009-02-19

  Compounds of formulas (A) and (B) are disclosed. The compounds of this invention are useful for ameliorating the side effects of therapeutic opiates.

  本发明揭示了化合物(A)和(B)的配方。本发明的化合物对于缓解治疗阿片类药物的副作用很有用。
• Substituted morphinans and methods of their use
  申请人：Dolle E. Roland

  公开号：US20060063792A1

  公开（公告）日：2006-03-23

  Novel 4,5-α epoxy-morphinan compounds are disclosed. Pharmaceutical compositions containing the 4,5-α epoxy-morphinan compounds and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

  揭示了新型的4,5-α环氧吗啡酮类化合物。还揭示了含有这些4,5-α环氧吗啡酮类化合物的药物组合物以及它们在药物用途中的方法。所揭示的化合物可作为阿片受体的调节剂等用途。