ethyl (2S,3S,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate | 1186028-94-3

• 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: ethyl (2S,3S,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate
• CAS: 1186028-94-3
• 化学式: C₂₅H₃₁NO₆
• 分子量: 441.524
• InChiKey: KUAPTDJZMCLPBZ-QWCHHGFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  80.76
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl (2S,3S,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate 、 苯胺 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到(4R,4aS,7S,7aR,12bS,14R)-3-(cyclopropylmethyl)-7-hydroxy-9-methoxy-N-phenyl-1,2,3,4,5,6,7,7a-octahydro-4a,7-(epoxymethano)-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carboxamide
  参考文献：
  名称：

  Drug design and synthesis of a novel κ opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology

  摘要：

  A conformational analysis of kappa opioid receptor agonists, TRK-820 and U-50,488H indicated an active conformation of TRK-820 in which the C-ring was in the boat form with the 14-OH interacting with the amide nitrogen. Based on the obtained active conformation of TRK-820, we designed and synthesized a novel kappa agonist KNT-63 with oxabicyclo[2.2.2]octane skeleton. KNT-63 showed profound antinociceptive effects via the kappa receptor which were as potent as that of TRK-820. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.027
• 作为产物：
  描述：

  纳曲酮EP杂质J 、 氯乙酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以48%的产率得到ethyl (2S,3R,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate
  参考文献：
  名称：

  Drug design and synthesis of a novel κ opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology

  摘要：

  A conformational analysis of kappa opioid receptor agonists, TRK-820 and U-50,488H indicated an active conformation of TRK-820 in which the C-ring was in the boat form with the 14-OH interacting with the amide nitrogen. Based on the obtained active conformation of TRK-820, we designed and synthesized a novel kappa agonist KNT-63 with oxabicyclo[2.2.2]octane skeleton. KNT-63 showed profound antinociceptive effects via the kappa receptor which were as potent as that of TRK-820. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.027