4,5α-epoxy-3,6α,14-trhydroxy-6βxmethyl-17(cyclopropylmethyl)morphinan | 55096-33-8

• 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: 4,5α-epoxy-3,6α,14-trhydroxy-6βxmethyl-17(cyclopropylmethyl)morphinan
• 英文别名: 17-cyclopropylmethyl-4,5α-epoxy-6-methyl-morphinane-3,6α,14-triol；6β-Methyl-6α-hydroxynaltrexon；6-methyl-α-naltrexol
• CAS: 55096-33-8
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: JWRHHLFJNSUSRN-OWYHGVQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  73.16
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  甲基锂 、 纳曲酮 以 乙醚 为溶剂， 反应 18.0h， 生成 4,5α-epoxy-3,6α,14-trhydroxy-6βxmethyl-17(cyclopropylmethyl)morphinan
  参考文献：
  名称：

  Narcotic antagonists. 4. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists

  摘要：

  A series of new narcotic antagonists has been synthesized by modifying the C-6 carbonyl group in naloxone (Ia) and naltrexone (Ib). New functional units were introduced by reaction with various phosphorus and sulfur ylides and alkyllithium reagents. The activity of the new compounds were measured by the hot-plate and tail-clip tests after oral administration to mice. The majority of the new narcotic antagonists exhibited oral potencies considerably superior to the parent compounds, with 6-methylene derivatives IIa and IIb showing the most impressive increases.

  DOI：

  10.1021/jm00237a008

文献信息

• Diastereomeric 6-desoxy-6-spiro-.alpha.-methylene-.gamma.-butyrolactone derivatives of naltrexone and oxymorphone. Selective irreversible inhibition of naltrexone binding in an opioid receptor preparation by a conformationally restricted Michael acceptor ligand
  作者：Gary A. Koolpe、Wendel L. Nelson、T. L. Gioannini、Lloyd Angel、Eric J. Simon

  DOI：10.1021/jm00378a032

  日期：1984.12

  naltrexone (4a and 5a) and of oxymorphone (4b and 5b) were prepared from their parent ketones. Diastereomers 4a and 4b were obtained from the 3,14-diacetate derivatives of naltrexone (6a) and oxymorphone (6b) by reaction with the Reformatsky reagent prepared from methyl alpha-(bromomethyl)acrylate. Deacetylation with methanol completed the synthesis. Diastereomers 5a and 5b were obtained from oxiranes 8a and

  纳曲酮（4a和5a）和羟吗啡酮（4b和5b）的非对映体6-脱氧-6-螺-α-亚甲基-γ-丁内酯衍生物是由其母体酮制备的。非对映体4a和4b通过与由α-（溴甲基）丙烯酸甲酯制备的Reformatsky试剂反应，从纳曲酮（6a）和羟吗啡酮（6b）的3，14-二乙酸酯衍生物获得。用甲醇脱乙酰完成合成。非对映异构体5a和5b分别从肟酮8a和8b获得。使环氧乙烷酮与乙酰乙酸乙酯的钠盐反应，然后进行甲基化和脱保护，分别完成5a和5b的合成。化合物5a是在阿片样物质放射性受体测定中与[3H]纳曲酮竞争中测试的最有效的药物。在5 nM的浓度下，该化合物产生50％的结合抑制。这种抑制作用的大部分（30％）是不可逆的，即，即使在存在和不存在Na +的情况下彻底清洗膜制剂后，这种抑制作用仍然存在。纳洛酮可以防止这种不可逆的作用。数据表明受体亲核试剂（可能是巯基）位于可以加成5a的α，β-不饱和羰基系统的位置。