4'a,9'-Dihydroxy-3'-methyl-1,1',2',3,3',4',4'a,5'-octahydrospiro[indene-2,6'-[4,12]methano[1]benzofuro[3,2-e]isoquinolin]-7'(7'aH)-one | 150380-34-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 4'a,9'-Dihydroxy-3'-methyl-1,1',2',3,3',4',4'a,5'-octahydrospiro[indene-2,6'-[4,12]methano[1]benzofuro[3,2-e]isoquinolin]-7'(7'aH)-one
• 英文别名: (4S,4aS,7aR)-4a,9-dihydroxy-3-methylspiro[1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6,2'-1,3-dihydroindene]-7-one
• CAS: 150380-34-0
• 化学式: C₂₅H₂₅NO₄
• 分子量: 403.5
• InChiKey: YJWDKWRVFJZBCJ-UOMUIJFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
  申请人：Waterville Valley Technologies, Inc.

  公开号：US20160326182A1

  公开（公告）日：2016-11-10

  Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.

  提供了耐滥用的阿片类化合物、药物输送系统、含有阿片类药物与化学基团共价结合的制药组合物。还提供了将活性成分输送给受试者的方法以及预防阿片类药物滥用的方法。
• [EN] NOVEL MIXED μ AGONIST/ δ ANTAGONIST OPIOID ANALGESICS WITH REDUCED TOLERANCE LIABILITIES AND USES THEREOF<br/>[FR] NOUVEAUX ANALGÉSIQUES OPIOÏDES MIXTES AGONISTES &Mgr; / ANTAGONISTES &Dgr; PRÉSENTANT MOINS D'INCONVÉNIENTS LIÉS À LA TOLÉRANCE ET LEURS UTILISATIONS
  申请人：UNIV MARYLAND

  公开号：WO2014138378A1

  公开（公告）日：2014-09-12

  An opioid narcotics used for the treatment of moderate-to-severe pain that primarily exert their analgesic effects through μ receptors. Although, traditional μ agonists can cause undesired side effects, including tolerance, addition of δ antagonists can attenuate said side effects. The present invention includes 4a,9-dihydroxy-7a-(hydroxymethyl)-3 -methyl-2,3,4,4a,5,6-hexahydro-1 H-4, 12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor, along with analogs of morphine, dihydromorphine, hydromorphone, codeine, dihydrocodeine, hydrocodone and ethylmorphine. Although UMB 425 lacks δ-specific motifs, conformationally sampled pharmacophore models for μ and δ receptors predict it to have efficacy similar to morphine at μ receptors and similar to naltrexone at δ receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. UMB 425 exhibits a mixed μ agonist/δ antagonist profile as determined in receptor binding. UMB 425 has mixed μ agonist/δ antagonist properties in vitro that translate to reduced tolerance liabilities in vivo.

  一种用于治疗中至重度疼痛的阿片类镇痛药物，主要通过μ受体发挥其镇痛作用。尽管传统的μ激动剂可能引起不良副作用，包括耐受性，但添加δ拮抗剂可以减轻这些副作用。本发明包括4a,9-二羟基-7a-(羟甲基)-3-甲基-2,3,4,4a,5,6-六氢-1 H-4,12-甲基苯并呋喃[3,2-e]异喹啉-7(7aH)-酮（UMB 425），一种基于5,14-桥联吗啡酮的奥维诺前体，以及吗啡、二氢吗啡、羟吗啡、可待因、二氢可待因、羟考酮和乙基吗啡的类似物。尽管UMB 425缺乏δ特异性基序，但μ和δ受体的构象采样药效模型预测其在μ受体上具有类似吗啡的功效，在δ受体上类似于纳曲酮，因为该化合物在构象采样中与受体相互作用的羟基部分类似于奥维诺酮。UMB 425在受体结合中表现出混合的μ激动剂/δ拮抗剂特性。UMB 425在体外表现出混合的μ激动剂/δ拮抗剂特性，这在体内转化为降低的耐受性风险。
• [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] MITRAGYNINE ALKALOIDS AS OPIOID RECEPTOR MODULATORS<br/>[FR] ALCALOÏDES DE TYPE MITRAGYNINE UTILISÉS COMME MODULATEURS DE RÉCEPTEURS OPIOÏDES
  申请人：UNIV COLUMBIA

  公开号：WO2017165738A1

  公开（公告）日：2017-09-28

  The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

  本发明提供一种具有以下结构的化合物：或其药用可接受的盐或酯，并通过向受痛苦、抑郁症、情绪障碍或焦虑障碍的对象施用该化合物的方法来治疗患者。
• [EN] CARBOXYLIC DIARYTHIAZEPINEAMINES AS MIXED MU-AND DELTA-OPIOID RECEPTOR AGONISTS<br/>[FR] DIARYTHIAZÉPINAMINES CARBOXYLIQUES EN TANT QU'AGONISTES MIXTES DE RÉCEPTEUR D'OPIOÏDE MU ET DELTA
  申请人：UNIV COLUMBIA

  公开号：WO2018170275A1

  公开（公告）日：2018-09-20

  The present invention provides a compound having the structure:, or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with a pain, a depressive disorder, a mood disorder, an anxiety disorder, borderline personality disorder, opioid addiction, or opioid withdrawal symptoms by administering the compound to the subject.

  本发明提供一种具有以下结构的化合物，或其药用可接受的盐或酯，以及通过向受到疼痛、抑郁障碍、情绪障碍、焦虑障碍、边缘人格障碍、阿片类成瘾或阿片类戒断症状困扰的对象施用该化合物的方法。