17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-(N-benzyloxycarbonyl)amine | 742104-55-8

• 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: 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-(N-benzyloxycarbonyl)amine
• CAS: 742104-55-8
• 化学式: C₃₂H₃₆N₂O₅
• 分子量: 528.648
• InChiKey: IIUYWGZXPNEUIE-CCRVCEFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  69.26
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-(N-benzyloxycarbonyl)amine 在 盐酸 、 溶剂黄146 作用下， 反应 1.0h， 以82%的产率得到(5α,7α)-17-(cyclopropylmethyl)-4,5-epoxy-3,6-dimethoxy-6,4-ethenomorphinan-7-amine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2004.05.024
• 作为产物：
  描述：

  N-(cyclopropylmethyl)northebaine 在 盐酸 、 一水合肼 、 sodium nitrite 作用下， 以 乙二醇乙醚 、 乙醚 、 水 为溶剂， 反应 46.5h， 生成 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-(N-benzyloxycarbonyl)amine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2004.05.024

文献信息

• 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.