(1S,2S,6R,14R,15S,16S)-5-(cyclopropylmethyl)-15-hydroxy-11-methoxy-N-phenyl-13,17-dioxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene-16-carboxamide | 1186029-01-5

• 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: (1S,2S,6R,14R,15S,16S)-5-(cyclopropylmethyl)-15-hydroxy-11-methoxy-N-phenyl-13,17-dioxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene-16-carboxamide
• CAS: 1186029-01-5
• 化学式: C₂₉H₃₂N₂O₅
• 分子量: 488.583
• InChiKey: RPIMUNPKEURPFQ-QAJOSVNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,2S,6R,14R,15S,16S)-5-(cyclopropylmethyl)-15-hydroxy-11-methoxy-N-phenyl-13,17-dioxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene-16-carboxamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到KNT-63
  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：

  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 、 苯胺 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以60%的产率得到(1S,2S,6R,14R,15S,16S)-5-(cyclopropylmethyl)-15-hydroxy-11-methoxy-N-phenyl-13,17-dioxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene-16-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

文献信息

• Rearrangement of 4,5α-epoxymorphinan derivatives with carbamoylepoxy rings provide novel oxazatricyclodecane structures
  作者：Kohei Hayashida、Hideaki Fujii、Shigeto Hirayama、Toru Nemoto、Hiroshi Nagase

  DOI：10.1016/j.tet.2011.04.097

  日期：2011.9

  We describe the rearrangement of a carbamoylepoxy 4,5α-epoxymorphinan derivative that provided a novel 4,5α-epoxymorphinan derivative with an oxazatricyclodecane structure via an oxabicyclo[2.2.2]octane intermediate. We proposed the mechanism of the rearrangement reaction based on results observed in different deprotonation conditions. Epimerization occurred during rearrangement under reversible, but

  我们描述了氨基甲酰环氧4,5α-环氧吗啡喃衍生物的重排，该衍生物通过氧杂双环[2.2.2]辛烷中间体提供具有氧杂三环癸烷结构的新型4,5α-环氧吗啡喃衍生物。我们基于在不同去质子化条件下观察到的结果提出了重排反应的机理。差向异构在重排过程中发生在可逆但不可逆的去质子化条件下。重排产物具有对阿片样物质受体具有中等亲和力的新颖基本结构（K i（μ）= 47.7 nM，K i（δ）= 174.6 nM和K i（κ）= 248.1 nM）。因此，重排产物作为阿片样物质配体可能具有高效力。