17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-phenethyl)carboxamide | 214064-41-2

• 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-dihydroxy-6,14-endoethenomorphinan-7α-(N-phenethyl)carboxamide
• 英文别名: (1R,2S,6R,14R,15R,16S)-5-(cyclopropylmethyl)-11,15-dihydroxy-N-(2-phenylethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraene-16-carboxamide
• CAS: 214064-41-2
• 化学式: C₃₁H₃₄N₂O₄
• 分子量: 498.622
• InChiKey: UEBANNTVMMEIPI-NPBSHTHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  82
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-phenethyl)carboxamide 在 palladium on activated charcoal 甲烷磺酸 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.32 kPa 条件下， 反应 20.0h， 以30%的产率得到17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethanomorphinan-7α-(N-phenethyl)carboxamide
  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：

  17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carboxylic acid monohydrochloride 在 草酰氯 、 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 4.0h， 生成 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-phenethyl)carboxamide
  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

• Rational drug design and synthesis of a selective ε opioid receptor antagonist on the basis of the accessory site concept
  作者：Hideaki Fujii、Minoru Narita、Hirokazu Mizoguchi、Junichi Hirokawa、Koji Kawai、Toshiaki Tanaka、Leon F Tseng、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2004.06.004

  日期：2004.8

  To newly synthesize a selective epsilon opioid receptor antagonist, 17-(cyclopropylmethyl)-4,5alpha-epoxy-6beta,21-epoxymethano-3hydroxy-6,14-endoethenomorphinan-7alpha-(N-phenethyl)carboxamide was first designed from an epsilon opioid receptor agonist TAN-821 on the basis of the accessory site concept. The designed compound antagonized the agonistic effects induced by an epsilon opioid receptor agonist beta-endorphin on the rat vas deference test. Moreover, the designed compound blocked the antinociception induced by beta-endorphin given intracerebroventricularly. (C) 2004 Elsevier Ltd. All rights reserved.