(4R,7aR,12bS)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one

• 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: (4R,7aR,12bS)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.34
• InChiKey: UQCNKQCJZOAFTQ-BOJGAVIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,7aR,12bS)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one 、 苯肼 生成 (4R,7E,7aR,12bS)-3-methyl-7-(phenylhydrazinylidene)-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
  参考文献：
  名称：

  HOSZTAFI, SANDOR;SZILAGYI, LASZLO;MAKLEIT, SANDOR;TOTH, GEZA, MAGY. KEM. FOLYOIR., 94,(1988) N 3, C. 121-126

  摘要：

  DOI：

文献信息

• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV MINNESOTA

  公开号：WO2016138142A1

  公开（公告）日：2016-09-01

  and salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods using a compound of formula I.

  其中的盐也被披露。还披露了包括I式化合物的药物组合物，用于制备I式化合物的过程，用于制备I式化合物的有用中间体以及使用I式化合物的治疗方法。
• [EN] PROCESS FOR THE PREPARATION OF OXYMORPHONE FREEBASE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'OXYMORPHONE SOUS FORME DE BASE LIBRE
  申请人：NORAMCO INC

  公开号：WO2016187522A1

  公开（公告）日：2016-11-24

  The present invention is directed to a process for the preparation oxymorphone freebase, comprising hydrogenation of 14-hydroxymorphinone in DMF, to yield oxymorphone freebase, preferably oxymorphone freebase of improved appearance, purity and / or yield. The present invention is further directed to oxymorphone freebase with improved impurity profile. The present invention is further directed to an HPLC or UPLC system/method for analysis of opioid compounds.

  本发明涉及一种制备羟吗啡自由基的方法，包括在DMF中对14-羟基吗啡酮进行氢化，得到羟吗啡自由基，优选具有改善外观、纯度和/或产率的羟吗啡自由基。本发明还涉及具有改善杂质谱的羟吗啡自由基。本发明还涉及用于分析阿片类化合物的HPLC或UPLC系统/方法。
• [EN] PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DE MORPHINANE
  申请人：SANECA PHARMACEUTICALS A S

  公开号：WO2019009820A1

  公开（公告）日：2019-01-10

  The invention describes the process of catalytic O-demethylation of 3-methoxy-morphinane compounds using boron tribromide. Addition of catalysts reduces the reaction time, improves reacting the substrate to give the product in very good purity and yield. The said approach can be used, for example, for the preparation of oxymorphone, naltrexone, naloxone and nalbuphine from their respective O-methyl derivatives.

  本发明描述了使用三溴化硼催化剂进行3-甲氧基吗啡烷类化合物的催化O-去甲基化过程。添加催化剂可缩短反应时间，提高底物的反应性，从而以非常高的纯度和收率给出产物。该方法可用于制备羟吗啡酮、纳曲酮、纳洛酮和纳布啡等化合物，这些化合物是从它们各自的O-甲基衍生物制备而来的。
• AMINO ACID PEPTIDE PRO-DRUGS OF PHENOLIC ANALGESICS AND USES THEREOF
  申请人：Franklin Richard

  公开号：US20090186832A1

  公开（公告）日：2009-07-23

  Prodrugs of meptazinol and other phenolic analgesics exhibiting low oral bioavailability with amino acids or lower peptides, pharmaceutical compositions containing such prodrugs and a method for providing pain relief with such prodrugs are provided. In addition, the present invention relates to methods for increasing the oral bioavailability of a phenolic analgesic. The method comprises orally administering a phenolic analgesic prodrug, wherein the phenolic analgesic is bound to an amino acid or peptide via a carbamate linkage, to a subject in need thereof. Prodrugs having side chains of valine, leucine, isoleucine and glycine amino acids and mono-, di- and tripeptides thereof are preferred.

  本发明提供了美托津诺尔及其他表现出口服生物利用度低的酚类镇痛剂的前药，其与氨基酸或较低的肽结合，以及含有这种前药的制药组合物和使用这种前药提供缓解疼痛的方法。此外，本发明还涉及提高酚类镇痛剂口服生物利用度的方法。该方法包括口服给予酚类镇痛剂前药，其中酚类镇痛剂通过氨基酸或肽的氨甲酰基链接结合到前药中，并给予需要的受试者。具有缬氨酸、亮氨酸、异亮氨酸和甘氨酸氨基酸和其单、二、三肽的侧链的前药是首选。
• COMPOSITIONS AND METHODS OF ENHANCING OPIOID RECEPTOR ENGAGEMENT BY OPIOID HEXADIENOATES AND OPTIONALLY SUBSTITUTED HEXADIENOATES
  申请人：Kappa-Pharma LLC

  公开号：US20200055864A1

  公开（公告）日：2020-02-20

  The present invention relates to opiate derived compositions and their antagonists useful in therapeutic areas associated with opioid receptor modulation, A 3-hexadienoate modification of the opioids is formulated to improve opiates' engagement of the opioid receptors when given orally. A 3-hexadienoate modification of Nalbuphine or a pharmaceutically acceptable salt of thereof to improve quality of pain management when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation. A 3-hexadienoate modification of the opioids antagonists is formulated to improve inhibition of the opioid receptors when given orally. A 3-hexadienoate modification of Naloxone or a pharmaceutically acceptable salt of thereof to improve quality of Sobering when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation.

  本发明涉及鸦片类化合物及其拮抗剂，用于调节与阿片受体相关的治疗领域。一种3-己二烯酸酯修饰的鸦片类化合物被设计用于口服时提高与阿片受体的结合能力。一种3-己二烯酸酯修饰的Nalbuphine或其药学上可接受的盐被设计用于静脉注射、鼻腔给药、经皮给药、舌下给药、直肠给药、局部给药、肌肉注射、皮下注射或吸入时提高镇痛疗效。一种3-己二烯酸酯修饰的鸦片类化合物的拮抗剂被设计用于口服时提高对阿片受体的抑制作用。一种3-己二烯酸酯修饰的Naloxone或其药学上可接受的盐被设计用于静脉注射、鼻腔给药、经皮给药、舌下给药、直肠给药、局部给药、肌肉注射、皮下注射或吸入时提高解酒疗效。