4,14-二羟基-3-甲氧基-17-甲基吗喃-6-酮 | 6199-38-8

• 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: 4,14-二羟基-3-甲氧基-17-甲基吗喃-6-酮
• 英文名称: 4,14β-dihydroxy-3-methoxy-17-methylmorphinan-6-one
• 英文别名: 14-hydroxydihydrothebainone；4,14-dihydroxy-3-methoxy-17-methyl-morphinan-6-one；4,14-Dihydroxy-3-methoxy-17-methyl-morphinan-6-on；Dihydrooxythebainon；14-Hydroxy-dihydro-thebainon；14-Hydroxy-dihydrothebainon；4,14-Dihydroxy-3-methoxy-N-methyl-6-oxomorphinan；(1R,9R,10S)-3,10-dihydroxy-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 6199-38-8
• 化学式: C₁₈H₂₃NO₄
• 分子量: 317.385
• InChiKey: MCSOAHVAIJXNDN-ZTFGCOKTSA-N

物化性质

• 熔点：
  142-145 °C
• 沸点：
  509.2±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,14-二羟基-3-甲氧基-17-甲基吗喃-6-酮 在 盐酸羟胺 、 水 作用下， 生成 4,14-dihydroxy-3-methoxy-17-methyl-morphinan-6-one oxime
  参考文献：
  名称：

  Freund; Speyer, Journal fur praktische Chemie (Leipzig 1954), 1916, vol. <2> 94, p. 156,157

  摘要：

  DOI：
• 作为产物：
  描述：

  盐酸羟可待酮 在 盐酸 、 溶剂黄146 、 锌 作用下， 反应 0.17h， 以71%的产率得到4,14-二羟基-3-甲氧基-17-甲基吗喃-6-酮
  参考文献：
  名称：

  δ Opioid Affinity and Selectivity of 4-Hydroxy-3-methoxyindolomorphinan Analogues Related to Naltrindole

  摘要：

  To investigate the effect of the introduction of a 4-phenolic substituent on the delta opioid affinity and selectivity of the indolomorphinans, a range of 4-phenolic analogues of naltrindole were prepared and evaluated in in vitro assays. Although the majority of the ligands displayed poor affinity for all three opioid receptors (mu, kappa, delta), 17-cyclopropylmethyl-6,7-didehydro-4-hydroxy-3-methoxy-6,7:2',3'-indolomorphinan (13) was an exception, displaying excellent delta binding selectivity (delta K-i = 7 nM, mu/delta = 1900, mu/kappa = 1130). GTP-gamma-S functional assays showed 13 to be a selective delta antagonist, albeit with lower potency than naltrindole. Although the reason for the unique profile of 13 could not be determined, these results validate our approach of introducing groups into the indolomorphinans that are known to reduce mu activity, to obtain increased delta selectivity.

  DOI：

  10.1021/jm9807003

文献信息

• Rapid access to morphinones: removal of 4,5-ether bridge with Pd-catalyzed triflate reduction
  作者：Christopher D. Hupp、John L. Neumeyer

  DOI：10.1016/j.tetlet.2010.02.146

  日期：2010.4

  A new synthetic method for the removal of the 4,5-bridged ether moiety of several opioids has been developed. This process offers a faster, simpler synthetic route to obtain the morphinone scaffold in high yields without the need for protection of the ketone moiety.

  已经开发出一种用于去除几种阿片类药物的 4,5-桥接醚部分的新合成方法。该过程提供了一种更快、更简单的合成途径，以高产率获得吗啡酮支架，而无需保护酮部分。
• Synthesis and opioid receptor activity of indolopropellanes
  作者：Fuying Li、Linghuan Gaob、Chenlei Yin、Jie Chen、Jinggen Liu、Xin Xie、Ao Zhang

  DOI：10.1016/j.bmcl.2009.06.093

  日期：2009.8

  displayed moderate binding affinity and selectivity at the μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioid receptors indicating a different interaction model existed.

  通过3-甲氧基-N-甲基-14-羟基吗啡喃-6-one 12的N-去甲基化，然后进行N-重烷基化，还原和Fischer吲哚环化，获得了一系列骨架重排的吲哚吗啡喃7a-d。通过X射线分析证实了该新型骨架的结构。这些新的吲哚在μ受体上表现出中等的结合亲和力和选择性，化合物7b在该受体上显示出最高亲和力，其K i值为40 nM，对δ和κ受体的选择性分别为6倍和25倍。功能测定表明吲哚丙二酮7b和7c 在所有阿片样物质受体上都具有完全激动作用，表明存在不同的相互作用模型。
• Syntheses of 4,6′-epoxymorphinan derivatives and their pharmacologies
  作者：Toru Nemoto、Hideaki Fujii、Minoru Narita、Kan Miyoshi、Atsushi Nakamura、Tsutomu Suzuki、Hiroshi Nagase

  DOI：10.1016/j.bmc.2008.02.082

  日期：2008.4

  A modi. cation of the message site in the skeleton of naltrexone was carried out to improve the potency and selectivity of the compound for an opioid receptor subtype. In the course of conversion, we synthesized 7-membered ring ether derivatives, which had an inserted OCH2 group between 4- and 6-positions of morphinan skeleton. One of the 7-membered ring ether derivatives possessed more potent antagonistic activity than naltrexone for the l opioid receptor. Another compound possessing 17-methyl group derived from noroxycodone may be a l opioid receptor partial agonist and showed analgesic activity. We are currently examining the subtype selectivity of these compounds. (C) 2008 Elsevier Ltd. All rights reserved.
• Gulland, Journal of the Chemical Society, 1928, p. 703
  作者：Gulland

  DOI：——

  日期：——
• Schoepf, Justus Liebigs Annalen der Chemie, 1927, vol. 452, p. 252
  作者：Schoepf

  DOI：——

  日期：——