ethyl 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carboxylate | 24997-66-8

• 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: ethyl 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carboxylate
• 英文别名: ethyl (5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,14-ethenomorphinan-7-carboxylate；17-cyclopropylmethyl-4,5α-epoxy-3,6-dimethoxy-6α,14α-etheno-morphinane-7α-carboxylic acid ethyl ester；ethyl (1R,2S,6R,14R,15R,16S)-5-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraene-16-carboxylate
• CAS: 24997-66-8
• 化学式: C₂₇H₃₃NO₅
• 分子量: 451.563
• InChiKey: FYQAWJHDXCARRE-QXIQULQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carboxylate 在 三溴化硼 、 水 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 17-cyclopropylmethyl-4,5α-epoxy-3,6-dihydroxy-6α,14α-etheno-morphinane-7α-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] BUPRENORPHINE ANALOGS
  [FR] ANALOGUES DE BUPRÉNORPHINE

  摘要：

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。

  公开号：

  WO2012038813A1
• 作为产物：
  描述：

  northebaine 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carboxylate
  参考文献：
  名称：

  [EN] BUPRENORPHINE ANALOGS
  [FR] ANALOGUES DE BUPRÉNORPHINE

  摘要：

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。

  公开号：

  WO2012038813A1

文献信息

• Novel analgesics and molecular rearrangements in the morphine–thebaine group. Part XVI. Some derivatives of 6,14-endo-etheno-7,8-dihydromorphine
  作者：K. W. Bentley、J. D. Bower、J. W. Lewis

  DOI：10.1039/j39690002569

  日期：——

  demethylated by hydrogen bromide in acetic acid to ethyl 6,14-endo-etheno-7,8-dihydromorphine-7α-carboxylate via the corresponding codeine derivative. 6,14-endo-Etheno-7,8-dihydro-7α(1-hydroxy-1-methylethyl)codeine is rearranged by base as well as by acid to a derivative of thebainone.

  通过乙酸中的溴化氢通过相应的可待因衍生物将6,14-内-乙基-四氢茶碱-7α-羧酸乙酯去甲基化为6,14-内-乙烯-7,8-二氢吗啡-7α-羧酸乙酯。6,14-内-Etheno -7,8-二氢7α（1-羟基-1-甲基乙基）可待因由碱以及由酸重新排列为一衍生物thebainone的。
• Novel rearrangement reaction of a 6,14-endoethanomorphinan derivative to a benzomorphan derivative
  作者：Hideaki Fujii、Yoshikazu Watanabe、Yumiko Osa、Toru Nemoto、Noriko Sato、Hiroshi Nagase

  DOI：10.1016/j.tet.2009.04.055

  日期：2009.6

  toluene reflux afforded a novel lactone by rearrangement reaction. The skeleton of the lactone is analogous to that of the benzomorphan like pentazocine, which is a useful analgesic. The rearrangement reaction opens the door to a facile synthesis from the 4,5-epoxymorphinans to the benzomorphan derivatives. On the basis of careful examination of the reaction intermediates, a reaction mechanism was

  在室温下用三氟甲磺酸酐处理7α-羟甲基内苯二氢吗啡喃衍生物，然后甲苯回流，通过重排反应得到新的内酯。内酯的骨架类似于苯并吗啡如喷他佐辛的骨架，它是有用的镇痛药。重排反应为从4,5-环氧吗啡喃到苯并吗啡啉衍生物的简便合成打开了大门。在仔细检查反应中间体的基础上，提出了反应机理。
• BUPRENORPHINE ANALOGS
  申请人：Kyle Donald J.

  公开号：US20140057931A1

  公开（公告）日：2014-02-27

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R 1 , R 2 , R 8 , R 3a , R 3 b , G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及以下式子所示的哌啶酯类似物化合物，其中R1、R2、R8、R3a、R3b、G、X、Z和Y如本文所定义。本发明的化合物可用于治疗疼痛、便秘和其他受到阿片类和ORL-1受体活性调节的病症。
• Drug design and synthesis of ε opioid receptor agonist: 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative ε opioid receptor
  作者：Hideaki Fujii、Minoru Narita、Hirokazu Mizoguchi、Miho Murachi、Toshiaki Tanaka、Koji Kawai、Leon F Tseng、Hiroshi Nagase

  DOI：10.1016/j.bmc.2004.05.024

  日期：2004.8.1

  Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative E: opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), showed agonistic activity for a putative E opioid receptor (IC50 = 71.71 nM) in the rat vas deferens (RVD) preparations. TAN-821 stimulated the binding of the nonhydrolyzable guanosine 5'-triphosphate analog, guanosine 5'-(gamma-thio)-triphosphate (GTPgammaS), to the mouse pons/medulla membrane via the activation of putative E: opioid receptor. Moreover, TAN-821 given intracerbroventricularly (i.c.v.) produced a marked antinociception in the tail-flick test (ED50 = 1.73 mug) and the hot-plate test (ED50 = 2.05 mug) in a dose-dependent manner. The antinociception induced by TAN-821 administered i.c.v. was blocked by the i.c.v.-pretreatment with a putative epsilon opioid receptor partial agonist beta-endorphin [1-27], but not a mu opioid receptor antagonist beta-FNA, a delta opioid receptor antagonist NTI, or a kappa opioid receptor antagonist nor-BNI. The present results suggest that TAN-821 may be a useful tool for the investigation on the pharmacological properties of the putative epsilon opioid receptor. (C) 2004 Elsevier Ltd. All rights reserved.
• Cinnamoyl Derivatives of 7α-Amino- and 7α-(Aminomethyl)-N-(cyclopropylmethyl)-6,14-endo-ethanotetrahydronororipavines are High-Potency Opioid Antagonists
  作者：Ian Derrick、Stephen M. Husbands、Jillian Broadbear、John R. Traynor、James H. Woods、John W. Lewis

  DOI：10.1002/1522-2675(20001220)83:12<3122::aid-hlca3122>3.0.co;2-2

  日期：2000.12.20