(-)-6-ethylenedioxy-14-hydroxy-3-methoxy-N-methylmorphinan | 21020-35-9

• 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: (-)-6-ethylenedioxy-14-hydroxy-3-methoxy-N-methylmorphinan
• 英文别名: 6,6-ethylenedioxy-3-methoxy-17-methylmorphinan-14β-ol；6,6-Ethylendioxy-14-hydroxy-3-methoxy-N-methyl-morphinan；6,6-ethane-1,2-diyldioxy-3-methoxy-17-methyl-morphinan-14-ol；14-Hydroxy-3-methoxy-17-methyl-6-oxo-morphinan 6-Ethylene Ketal；(1'R,9'R,10'S)-4'-methoxy-17'-methylspiro[1,3-dioxolane-2,13'-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene]-10'-ol
• CAS: 21020-35-9
• 化学式: C₂₀H₂₇NO₄
• 分子量: 345.439
• InChiKey: SSKUWIKLIAYCJP-QWFCFKBJSA-N

物化性质

• 熔点：
  168-169 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  502.9±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (-)-6-ethylenedioxy-14-hydroxy-3-methoxy-N-methylmorphinan 在 氢溴酸 、 pyridinium hydrobromide perbromide 作用下， 以 溶剂黄146 为溶剂， 反应 0.25h， 生成 (-)-7α-bromo-14-hydroxy-3-methoxy-6-oxo-N-methylmorphinan
  参考文献：
  名称：

  Sawa, Yoshiro K.; Kobayashi, Masaaki; Tada, Haruhiko, Heterocycles, 1984, vol. 22, # 11, p. 2575 - 2579

  摘要：

  DOI：
• 作为产物：
  描述：

  6,6-ethylenedioxy-3-methoxy-17-(2,2,2-trichloroethoxycarbonyl)morphinan-14β-yl acetate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以76%的产率得到(-)-6-ethylenedioxy-14-hydroxy-3-methoxy-N-methylmorphinan
  参考文献：
  名称：

  Synthesis of quinolinomorphinan derivatives as highly selective δ opioid receptor ligands

  摘要：

  We have reported previously the novel delta opioid agonist KNT-127 which showed high affinity and selectivity for the delta receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical delta agonist (-)-TAN-67 in the acetic acid writhing test. This study of the structure-activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5'-, 6'-, 7'- or 8'-position of the quinoline ring and revealed that many derivatives with 5'- or 8'-substituents showed high affinities and selectivities for the delta receptor. Especially, SYK-153 with an 8'-OH group showed the highest affinity and the most balanced and highest selectivity for the delta receptor among the synthesized compounds. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.004

文献信息

• [EN] AZAMOPHINAN DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS D'AZAMOPHINAN ET LEUR UTILISATION
  申请人：PURDUE PHARMA LP

  公开号：WO2015192053A1

  公开（公告）日：2015-12-17

  The application is directed to compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, Y, and Z are defined as set forth in the specification. The invention is also directed to use of compounds of any one of Formulae I-VIII, and the pharmaceutically acceptable salts and solvates thereof, to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the invention are especially useful for treating pain.

  该应用程序涉及公式（I）的化合物及其药用可接受的盐和溶剂化合物，其中R1、R2、R3、R4、Y和Z的定义如规范中所述。该发明还涉及使用任一公式I-VIII的化合物及其药用可接受的盐和溶剂化合物来治疗对调节一个或多个阿片受体敏感的疾病，或作为合成中间体。该发明的某些化合物特别适用于治疗疼痛。
• Elimination of the 4-hydroxyl group of the alkaloids related to morphine—XI
  作者：Y.K. Sawa、H. Tada

  DOI：10.1016/s0040-4020(01)96351-3

  日期：1968.1

  Ullmann reaction of 14-hydroxydihydrothebainone followed by sodium liquid ammonia reduction gave (—)-14-hydroxy-3-methoxy-6-oxo-N-methylmorphinan in high yield. Starting from this compound 6-methyl derivatives were synthesized.

  14-羟基二氢蒂巴酮的乌尔曼反应，然后将钠液氨还原，以高收率得到（-）-14-羟基-3-甲氧基-6-氧代-N-甲基吗啡喃。从该化合物开始，合成了6-甲基衍生物。
• 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。
• Azamorphinan derivatives and use thereof
  申请人：Purdue Pharma L.P.

  公开号：US10202382B2

  公开（公告）日：2019-02-12

  The application is directed to compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, Y, and Z are defined as set forth in the specification. The invention is also directed to use of compounds of any one of Formulae I-VIII, and the pharmaceutically acceptable salts and solvates thereof, to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the invention are especially useful for treating pain.

  本申请涉及式（I）化合物及其药学上可接受的盐和溶液，其中 R1、R2、R3、R4、Y 和 Z 的定义如说明书所述。本发明还涉及使用式 I-VIII 中任一项的化合物及其药学上可接受的盐和溶液来治疗对一种或多种阿片受体的调节有反应的疾病，或作为合成中间体。本发明的某些化合物尤其适用于治疗疼痛。
• Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration
  作者：Hiroshi Nagase、Toru Nemoto、Ayaka Matsubara、Manabu Saito、Naoshi Yamamoto、Yumiko Osa、Shigeto Hirayama、Mayumi Nakajima、Kaoru Nakao、Hidenori Mochizuki、Hideaki Fujii

  DOI：10.1016/j.bmcl.2010.08.083

  日期：2010.11

  We have reported previously the novel delta-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype delta-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30 mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel delta-agonist, KNT-127, which was effective with systemic administration. (C) 2010 Elsevier Ltd. All rights reserved.