MCL-691 | 1310086-72-6

• 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: MCL-691
• 英文别名: (-)-14-Methoxybutorphanol；(1S,9R,10S)-17-(cyclobutylmethyl)-10-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol
• CAS: 1310086-72-6
• 化学式: C₂₂H₃₁NO₂
• 分子量: 341.494
• InChiKey: AVDWHTCJIXKWKF-BHIFYINESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  MCL-691 在 4-二甲氨基吡啶 、 palladium on carbon 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (5α)-17-allyl-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-yl 14-methoxy-N-cyclobutylmethylmorphinan-3-yl decanedioate
  参考文献：
  名称：

  Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors

  摘要：

  A novel series of homo-and heterodimeric ligands containing kappa/mu agonist and mu agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at kappa, mu, and delta opioid receptors, and their functional activities were determined at kappa and mu receptors in [S-35] GTP gamma S functional assays. Most of these compounds had high binding affinity at mu and kappa receptors (K-i values less than 1 nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity K-i values of 0.089 nM at the mu receptor and 0.073 nM at the kappa receptor. All of the morphinan-derived ligands were found to be partial kappa and mu agonists; ATPM-derived ligands 12 and 11 were found to be full kappa agonists and partial mu agonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.052
• 作为产物：
  描述：

  布托啡诺 在 palladium on carbon 、 氢气 、 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.25h， 生成 MCL-691
  参考文献：
  名称：

  Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors

  摘要：

  A novel series of homo-and heterodimeric ligands containing kappa/mu agonist and mu agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at kappa, mu, and delta opioid receptors, and their functional activities were determined at kappa and mu receptors in [S-35] GTP gamma S functional assays. Most of these compounds had high binding affinity at mu and kappa receptors (K-i values less than 1 nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity K-i values of 0.089 nM at the mu receptor and 0.073 nM at the kappa receptor. All of the morphinan-derived ligands were found to be partial kappa and mu agonists; ATPM-derived ligands 12 and 11 were found to be full kappa agonists and partial mu agonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.052

文献信息

• Oxycodone conjugates with lower abuse potential and extended duration of action
  申请人：Controlled Chemicals, Inc.

  公开号：EP1782834A2

  公开（公告）日：2007-05-09

  The abuse potential of a bioavailable drug such as an opiate analgesic agent is reduced and its duration of action is extended by converting it to a poorly absorbed ester prodrug derivative prior to formulation. Unlike many existing sustained release formulations of active pharmaceutical agents wherein an active pharmaceutical agent can be released by chewing, crushing or otherwise breaking tablets or capsule beads containing the active pharmaceutical agent, such mechanical processing of tablets or capsule beads containing a prodrug of this invention neither releases the active drug nor compromises the controlled conversion of prodrug to drug. Moreover, tablets and capsule beads containing prodrugs of this invention or other drugs can be formulated with a sufficient amount of a thickening agent such as hydroxypropylmethylcellulose to impede inappropriate intravenous and nasal administration of formulations that are not indicated for these modes of administration.

  通过在配制前将生物可利用药物（如阿片类镇痛剂）转化为吸收性较差的酯类原药衍生物，可降低其滥用可能性并延长其作用时间。与许多现有的活性药剂缓释制剂不同，含有本发明原药的片剂或胶囊珠通过咀嚼、碾碎或其他方式破碎，活性药剂就会释放出来，而对含有本发明原药的片剂或胶囊珠进行这种机械加工，既不会释放出活性药物，也不会影响原药向药物的可控转化。此外，含有本发明原药或其他药物的片剂和胶囊珠剂可以配制足量的增稠剂，如羟丙基甲基纤维素，以防止不适合静脉注射和鼻腔给药的制剂，因为这些制剂并不适用于这些给药方式。
• Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors
  作者：Bin Zhang、Tangzhi Zhang、Anna W. Sromek、Thomas Scrimale、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1016/j.bmc.2011.03.052

  日期：2011.5

  A novel series of homo-and heterodimeric ligands containing kappa/mu agonist and mu agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at kappa, mu, and delta opioid receptors, and their functional activities were determined at kappa and mu receptors in [S-35] GTP gamma S functional assays. Most of these compounds had high binding affinity at mu and kappa receptors (K-i values less than 1 nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity K-i values of 0.089 nM at the mu receptor and 0.073 nM at the kappa receptor. All of the morphinan-derived ligands were found to be partial kappa and mu agonists; ATPM-derived ligands 12 and 11 were found to be full kappa agonists and partial mu agonists. (C) 2011 Elsevier Ltd. All rights reserved.