纳曲酮杂质 | 96445-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 纳曲酮杂质
• 英文名称: 17-(cyclopropylmethyl)-4,5α-epoxy-14β-hydroxy-3-methoxymorphinan-6,10-dione
• 英文别名: 10-ketonaltrexone 3-methyl ether；10-Oxo-3-O-methylnaltrexone；(4S,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxy-1,2,4,5,6,7a-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7,13-dione
• CAS: 96445-13-5
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: MPULCDMBFAYJIX-IVAOSVALSA-N

物化性质

• 熔点：
  90-95°C
• 溶解度：
  溶于二氯甲烷、DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  纳曲酮杂质 在 palladium on activated charcoal sodium hydroxide 、 sodium tetrahydroborate 、 氢气 、 四丁基碘化铵 、 sodium carbonate 、 溶剂黄146 、 三乙胺 、 邻苯二甲酸 、 苯甲酸 、 1-丙烷硫醇钠 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 124.67h， 生成 (E)-N-[10α-acetoxy-3-tert-butoxycarbonyloxy-17-(cyclopropylmethyl)-4,5α-epoxy-14β-hydroxymorphinan-6β-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
  参考文献：
  名称：

  Syntheses of 10-Oxo, 10.ALPHA.-Hydroxy, and 10.BETA.-Hydroxy Derivatives of a Potent .KAPPA.-Opioid Receptor Agonist, TRK-820

  摘要：

  描述了强效κ-阿片受体选择性激动剂TRK-820的10-氧、10α-羟基和10β-羟基衍生物的合成。这些衍生物被认为是TRK-820在制剂中的潜在降解产物，源于自氧化。10-氧-TRK-820 11是通过10步反应，从10-氧-4,5-环氧吗啡烷14合成而得，整体产率为32%。用NaBH4还原4,5-环氧吗啡烷中的10-氧基团，得到的完全是10β-羟基-4,5-环氧吗啡烷。建立了一种逐步反转10β-羟基的方法，以合成10α-羟基-4,5-环氧吗啡烷。通过高效液相色谱（HPLC）分析，确认10α-羟基-TRK-820 12是TRK-820开发制剂中的降解产物之一。

  DOI：

  10.1248/cpb.52.664
• 作为产物：
  描述：

  纳曲酮EP杂质J 在 chromium(VI) oxide 、 CrO₃-DMP 、 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 28.25h， 生成 纳曲酮杂质
  参考文献：
  名称：

  10-Ketonaltrexone and 10-ketooxymorphone

  摘要：

  Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone (2) and oxymorphone (3) at mu sites and also had little affinity for kappa and delta sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.

  DOI：

  10.1021/jm00145a024

文献信息

• Syntheses of 10-Oxo, 10.ALPHA.-Hydroxy, and 10.BETA.-Hydroxy Derivatives of a Potent .KAPPA.-Opioid Receptor Agonist, TRK-820
  作者：Hiromasa Horikiri、Noriyuki Hirano、Yoichiro Tanaka、Junji Oishi、Hitoshi Hatakeyama、Kuniaki Kawamura、Hiroshi Nagase

  DOI：10.1248/cpb.52.664

  日期：——

  Syntheses of 10-oxo, 10α-hydroxy, and 10β-hydroxy derivatives of a potent κ-opioid receptor selective agonist, TRK-820, are described. These derivatives were supposed to be potential degradation products in formulation of TRK-820 as a result of autoxidation. 10-Oxo-TRK-820 11 was derived from 10-oxo-4,5-epoxymorphinan 14 in 10 steps in 32% overall yield. Reduction of the 10-oxo group in 4,5-epoxymorphinan with NaBH4 gave 10β-hydroxy-4,5-epoxymorphinan, exclusively. A stepwise inversion method of the 10β-hydroxy group to produce 10α-hydroxy-4,5-epoxymorphinan was established. By HPLC analyses, 10α-hydroxy-TRK-820 12 was confirmed to be one of the degradation products in developing formulation of TRK-820.

  描述了强效κ-阿片受体选择性激动剂TRK-820的10-氧、10α-羟基和10β-羟基衍生物的合成。这些衍生物被认为是TRK-820在制剂中的潜在降解产物，源于自氧化。10-氧-TRK-820 11是通过10步反应，从10-氧-4,5-环氧吗啡烷14合成而得，整体产率为32%。用NaBH4还原4,5-环氧吗啡烷中的10-氧基团，得到的完全是10β-羟基-4,5-环氧吗啡烷。建立了一种逐步反转10β-羟基的方法，以合成10α-羟基-4,5-环氧吗啡烷。通过高效液相色谱（HPLC）分析，确认10α-羟基-TRK-820 12是TRK-820开发制剂中的降解产物之一。
• 10-Ketonaltrexone and 10-ketooxymorphone
  作者：Sydney Archer、Ahmad Seyed-Mozaffari、Susan Ward、Hans W. Kosterlitz、Stewart J. Paterson、Alexander T. McKnight、Alistair D. Corbett

  DOI：10.1021/jm00145a024

  日期：1985.7

  Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone (2) and oxymorphone (3) at mu sites and also had little affinity for kappa and delta sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.