14-O-Me-codeinone | 32470-91-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 14-O-Me-codeinone
• 英文别名: 4,5α-epoxy-3,14-dimethoxy-17-methyl-(14ξ)-morphin-7-en-6-one；(4R,7aR,12bS)-4a,9-dimethoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 32470-91-0
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: YUGMSZACTDKLDJ-QPZJVUEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  14-O-Me-codeinone 生成 (4R,7aR,12bS)-4a,9-dimethoxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
  参考文献：
  名称：

  GHOSH, A. C.;RAZDAN, R. K.

  摘要：

  DOI：
• 作为产物：
  描述：

  14β-Hydroxy-codeinon 生成 14-O-Me-codeinone
  参考文献：
  名称：

  GHOSH, A. C.;RAZDAN, R. K.

  摘要：

  DOI：

文献信息

• A Novel µ-Opioid Receptor Ligand with High In Vitro and In Vivo Agonist Efficacy
  作者：E. Lacko、A. Varadi、R. Rapavi、F. Zador、P. Riba、S. Benyhe、A. Borsodi、S. Hosztafi、J. Timar、B. Noszal、S. Furst、M. Al-Khrasani

  DOI：10.2174/092986712803306376

  日期：2012.10.1

  The aims of this study were to synthesize 14-O-Methylmorphine-6-O-sulfate (14-O-MeM6SU) and examine its opioid properties (potency, affinity, efficacy) in receptor ligand binding and isolated tissues (mouse vas deferens, MVD and rat vas deferens, RVD bioassays). The results were then compared to the parent compounds morphine-6-O-sulfate (M6SU) and morphine, as well as the µ- opioid receptor (MOR) selective agonist peptide [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO). An additional objective was to compare the effect of subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) administered 14-O-MeM6SU, M6SU and morphine in thermal nociception, rat tail-flick (RTF) test. In MVD, the EC50 (nM) value was 4.38 for 14-O-MeM6SU, 102.81 for M6SU, 346.63 for morphine and 238.47 for DAMGO. The effect of 14-O-MeM6SU and DAMGO was antagonized by naloxone (NAL) with Ke value 1-2.00 nM. The Emax values (%) were 99.10, 36.87, 42.51 and 96.99 for 14-O-MeM6SU, M6SU, morphine and DAMGO, respectively. In RVD 14-O-MeM6SU and DAMGO but not M6SU or morphine showed agonist activity. In binding experiments the affinity of 14-OMeM6SU, M6SU, morphine and DAMGO for MOR was 1.12, 11.48, 4.37 and 3.24 nM, respectively. The selectivity of 14-O-MeM6SU was κ/μ= 269 and δ/μ= 9. In G-protein activation experiments, 14-O-MeM6SU and DAMGO showed higher Emax values than M6SU or morphine. S.c. or i.c.v-injected 14-O-MeM6SU, M6SU and morphine produced a dose and time-dependent increase in RTF response latency. 14-O-MeM6SU was the most potent. Our results showed that introduction of 14-O-Me in M6SU increased the binding affinity, agonist potency, and most importantly, the intrinsic efficacy (Emax).

  本研究旨在合成14-O-甲基吗啡-6-O-磺酸酯（14-O-MeM6SU），并检测其在受体配体结合及离体组织（小鼠输精管MVD和鼠输精管RVD生物测定）中的阿片样性质（效能、亲和力、效价）。然后将结果与母体化合物吗啡-6-O-磺酸酯（M6SU）和吗啡以及μ-阿片受体（MOR）选择性激动剂肽[D-Ala2,N-Me-Phe4,Gly-ol5]脑啡肽（DAMGO）进行比较。另外的目标是比较皮下注射（s.c.）或脑室内注射（i.c.v.）14-O-MeM6SU、M6SU和吗啡对热痛觉的作用，使用大鼠甩尾试验（RTF）。在MVD中，EC50（nM）值分别为14-O-MeM6SU的4.38，M6SU的102.81，吗啡的346.63，以及DAMGO的238.47。14-O-MeM6SU和DAMGO的作用被纳洛酮（NAL）阻断，K值为1-2.00 nM。Emax值（%）分别为14-O-MeM6SU的99.10，M6SU的36.87，吗啡的42.51，以及DAMGO的96.99。在RVD中，14-O-MeM6SU和DAMGO显示激动剂活性，而M6SU和吗啡不显示。在结合实验中，14-O-MeM6SU、M6SU、吗啡和DAMGO对MOR的亲和力分别为1.12、11.48、4.37和3.24 nM。14-O-MeM6SU的选择性为κ/μ= 269和δ/μ= 9。在G-蛋白激活实验中，14-O-MeM6SU和DAMGO显示出比M6SU或吗啡更高的Emax值。皮下或脑室内注射14-O-MeM6SU、M6SU和吗啡产生剂量和时间依赖性的RTF反应延迟增加。14-O-MeM6SU最为强效。我们的结果表明，在M6SU中引入14-O-Me增加了结合亲和力，激动剂效能，最重要的是，内在效价（Emax）。