(5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan-7-amine | 102746-08-7

• 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: (5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan-7-amine
• 英文别名: 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-amine；(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-tetraen-16-amine
• CAS: 102746-08-7
• 化学式: C₂₄H₃₀N₂O₃
• 分子量: 394.514
• InChiKey: RTXWZMUWLWSAJK-GCRRLYLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  56.95
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan-7-amine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 13.0h， 以95%的产率得到(5α,7α)-7-amino-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan
  参考文献：
  名称：

  Cinnamoyl Derivatives of 7α-Amino- and 7α-(Aminomethyl)-N-(cyclopropylmethyl)-6,14-endo-ethanotetrahydronororipavines are High-Potency Opioid Antagonists

  摘要：

  DOI：

  10.1002/1522-2675(20001220)83:12<3122::aid-hlca3122>3.0.co;2-2
• 作为产物：
  描述：

  7α-acetyl-17-cyclopropylmethyl-6,14-endo(etheno)tetrahydronorthebaine 在 盐酸 、 sodium azide 作用下， 以 高氯酸 为溶剂， 反应 27.0h， 生成 (5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan-7-amine
  参考文献：
  名称：

  Cinnamoyl Derivatives of 7α-Amino- and 7α-(Aminomethyl)-N-(cyclopropylmethyl)-6,14-endo-ethanotetrahydronororipavines are High-Potency Opioid Antagonists

  摘要：

  DOI：

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

文献信息

• Probes for narcotic receptor mediated phenomena. 13. Potential irreversible narcotic antagonist-based ligands derived from 6,14-endo-ethenotetrahydrooripavine with 7-(methoxyfumaroyl)amino, (bromoacetyl)amino, or isothiocyanate electrophiles: chemistry, biochemistry, and pharmacology
  作者：Ralph A. Lessor、Balbir S. Bajwa、Kenner C. Rice、Arthur E. Jacobson、Richard A. Streaty、Werner A. Klee、Charles B. Smith、Mario D. Aceto、Everette L. May、Louis S. Harris

  DOI：10.1021/jm00161a002

  日期：1986.11

  (methoxyfumaroyl)amino) and examined in vivo for their narcotic agonist and antagonist activities and for their ability to interact with opioid receptors in vitro. The N-(cyclopropylmethyl)-substituted compounds were found to have the highest affinity for opioid receptors among these N-substituted compounds, although all of them were found to be reasonably potent narcotic antagonists in the mouse tail flick vs. morphine

  合成了N-烯丙基-，N-（环丙基甲基）-和N-丙基-内酯-乙炔四氢去甲肾上腺素（N-取代的6,14-内酯-乙炔-4,5-环氧-3-羟基-6-甲氧基吗啡喃）将C-7位上的部分酰化或烷基化（异硫氰酸根，（溴乙酰基）氨基和（甲氧基富马酰基）氨基），并在体内检查其麻醉激动剂和拮抗剂活性，以及​​它们与阿片受体在体外相互作用的能力。在这些N-取代的化合物中，发现N-（环丙基甲基）-取代的化合物对阿片受体具有最高的亲和力，尽管在小鼠甩尾vs吗啡试验中发现它们都是相当有效的麻醉剂。在小鼠静脉内注射时，它们的体内效力是纳洛啡的1/8至4倍。大鼠脑膜结合研究表明，该化合物与阿片受体相互作用的效力范围为吗啡（8c，9c和10c）的0.5倍至吗啡（8b）的0.017。在使用NG108-15神经母细胞瘤-神经胶质瘤杂交细胞和/或使用NG108-15神经母细胞瘤和//或在大鼠脑膜制剂中。发现8c和10c在一定程度上
• 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.