(-)-4,5-epoxy-3-hydroxy-N-(2,2,2-trichloroethoxycarbonyl)morphinan-6-one | 85618-66-2

• 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: (-)-4,5-epoxy-3-hydroxy-N-(2,2,2-trichloroethoxycarbonyl)morphinan-6-one
• CAS: 85618-66-2
• 化学式: C₁₉H₁₈Cl₃NO₅
• 分子量: 446.715
• InChiKey: KGCMSGOWVHQCGH-YYNKCLGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  28.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  76.07
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (-)-4,5-epoxy-3-hydroxy-N-(2,2,2-trichloroethoxycarbonyl)morphinan-6-one 在 sodium dihydrogenphosphate 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 Norhydromorphone
  参考文献：
  名称：

  Identification and synthesis of norhydromorphone, and determination of antinociceptive activities in the rat formalin test

  摘要：

  The main objective of this paper is to report the identification and synthesis of norhydromorphone, a novel metabolite of hydromorphone, and its antinociceptive activities when tested in the formalin test as compared to other known analgesics. In addition, we are reporting for the first time the lack of antinociceptive activities of hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide in the rat formalin test. Norhydromorphone was isolated and identified as a metabolite of hydromorphone in a cancer patient's urine. An authentic standard of norhydromorphone was synthesized. The identity of norhydromorphone in the urine sample was confirmed by comparing the LC retention time and MS ion fragmentation with the synthetic standard using a liquid chromatographic-mass spectrometric-mass spectrometric (LC-MS-MS) assay. Norhydromorphone was found to be a minor metabolite of hydromorphone in the urine. Additionally, the antinociceptive activities of norhydromorphone, hydromorphone, morphine, dihydromorphine, dihydroisomorphine, hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were determined in the rat formalin test following intraperitoneal (i.p.) administration. Only limited antinociception was observed and no significant increase in antinociception was detected at the three doses tested. The increased polarity of norhydromorphone as compared to hydromorphone due to the primary piperidine nitrogen may make it less favorable to cross the blood-brain-barrier (BBB), which may be partly responsible. In addition, lower intrinsic antinociceptive activity, which remains to be determined, could also contribute to the low antinociception. Our results also show that hydromorphone was five times as potent as morphine in the formalin test, while dihydromorphine and dihydroisomorphine were equipotent to and 36% as potent as morphine, respectively. Hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide did not exhibit any antinociceptive effect at the doses tested. The results further underscore the importance of a free C-3-OH to the analgesic effect of morphine alkaloids. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.lfs.2004.06.008
• 作为产物：
  描述：

  氢吗啡酮 、 氯甲酸-2,2,2-三氯乙酯 在 氢氧化钾 、 potassium hydrogencarbonate 作用下， 生成 (-)-4,5-epoxy-3-hydroxy-N-(2,2,2-trichloroethoxycarbonyl)morphinan-6-one
  参考文献：
  名称：

  氧化吗啡的结构-活性关系。七。4-羟基和3,4-二加氧的6-吗啡酮系列的5-甲基化和14-羟基取代的激动剂和拮抗剂

  摘要：

  通过常规化学方法制备了几种在C（3），C（4），C（5）和C（14）处不同取代的吗啡酮激动剂以及4-羟基和3,4-二甲氧基系列的拮抗剂。事实证明，海湾区域的氧化模式非常重要，包括C（3）和C（4）。C（5）处的烷基化或C（14）处的羟基化降低了化合物的效力。发现最有效的激动剂是N-苯乙基取代的酮27，其在热板测定中的效力是吗啡的六倍。3，4-亚甲基二氧基取代的酮9的效力比其3，4-二甲氧基同类物低约20倍。X射线分析9 且有代表性的激动剂表明，海湾地区的立体化学特征相似，因此不能用来解释这种差异。

  DOI：

  10.1002/hlca.19820650804