14-Acetoxy-17-(cyclopropylmethyl)-3-hydroxy-6-oxo-4,5α-epoxymorphinan | 121962-99-0

• 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: 14-Acetoxy-17-(cyclopropylmethyl)-3-hydroxy-6-oxo-4,5α-epoxymorphinan
• 英文别名: 14-acetoxy-17-(cyclopropylmethyl)-4,5α-epoxy-3-hydroxymorphinan-6-one；naltrexone 14-acetate；14-acetoxy-17-cyclopropylmethyl-3-hydroxy-4,5α-epoxy-morphinan-6-one；[(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl] acetate
• CAS: 121962-99-0
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: KNZUMVWQRHFBQF-KDXIVRHGSA-N

物化性质

• 熔点：
  205-207 °C(Solv: methanol (67-56-1))
• 沸点：
  553.0±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  14-Acetoxy-17-(cyclopropylmethyl)-3-hydroxy-6-oxo-4,5α-epoxymorphinan 在 ammonium hydroxide 、 硫酸 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以50%的产率得到naltrexone 3-sulfate 14-acetate ammonium salt
  参考文献：
  名称：

  Synthesis and biological activity of the phosphate and sulfate esters of naloxone and naltrexone

  摘要：

  Prodrugs of the two opiate antagonists naloxone and naltrexone, in particular the 3-monophosphate, 3-triphosphate, 9-monosulfate and 3,l4-disulfate eaters, have been synthesized and evaluated for: i) their ability to bind opioid receptors in vitro; and ii) their stability in both space and time upon entrapment into ex vivo human red blood cells (RBC). We find that, unlike the other esters, the mono- and triphosphate eaters of naloxone and naltrexone retain high (in the nmol range) affinities especially for mu- and kappa-opioid receptors. Owing to their hydrophilic nature, the two esters could possibly help in certain types of pharmacological experiments. Moreover, upon entrapment into human RBC, the triphosphate esters of naloxone and naltrexone display considerable ex vivo intracellular stability.

  DOI：

  10.1016/0223-5234(94)90125-2
• 作为产物：
  描述：

  纳曲酮 在 硫酸 作用下， 反应 25.0h， 生成 14-Acetoxy-17-(cyclopropylmethyl)-3-hydroxy-6-oxo-4,5α-epoxymorphinan
  参考文献：
  名称：

  Synthesis and biological activity of the phosphate and sulfate esters of naloxone and naltrexone

  摘要：

  Prodrugs of the two opiate antagonists naloxone and naltrexone, in particular the 3-monophosphate, 3-triphosphate, 9-monosulfate and 3,l4-disulfate eaters, have been synthesized and evaluated for: i) their ability to bind opioid receptors in vitro; and ii) their stability in both space and time upon entrapment into ex vivo human red blood cells (RBC). We find that, unlike the other esters, the mono- and triphosphate eaters of naloxone and naltrexone retain high (in the nmol range) affinities especially for mu- and kappa-opioid receptors. Owing to their hydrophilic nature, the two esters could possibly help in certain types of pharmacological experiments. Moreover, upon entrapment into human RBC, the triphosphate esters of naloxone and naltrexone display considerable ex vivo intracellular stability.

  DOI：

  10.1016/0223-5234(94)90125-2

文献信息

• The facility of formation of a .DELTA.6 bond in dihydromorphinone and related opiates
  作者：Hiroshi Nagase、Akira Abe、Philip S. Portoghese

  DOI：10.1021/jo00278a025

  日期：1989.8
• Facile intramolecular oxygen-14 .fwdarw. carbon-7 acetyl transfer in opiate 14-acetate esters
  作者：H. Nagase、P. S. Portoghese

  DOI：10.1021/jo00288a068

  日期：1990.1
• Ring C conformation of 6.beta.-naltrexol and 6.alpha.-naltrexol. Evidence from proton and carbon-13 nuclear magnetic resonance
  作者：George A. Brine、Doriswamy Prakash、Carolyn King Hart、Dennis J. Kotchmar、Charles G. Moreland、Frank I. Carroll

  DOI：10.1021/jo00883a027

  日期：1976.10
• NAGASE, HIROSHI;ABE, AKIRA;PORTOGHESE, PHILIP S., J. ORG. CHEM., 54,(1989) N7, C. 4120-4125
  作者：NAGASE, HIROSHI、ABE, AKIRA、PORTOGHESE, PHILIP S.

  DOI：——

  日期：——
• NAGASE, H.;PORTOGHESE, P. S., J. ORG. CHEM., 55,(1990) N, C. 365-367
  作者：NAGASE, H.、PORTOGHESE, P. S.

  DOI：——

  日期：——