N-[(2S,4aS,7aR,12aR,14R)-5-(cyclopropylmethyl)-9-hydroxy-2,3,4,4a,5,6,7,12-octahydro-1H-2,7a-ethanoindeno[1,2-d]quinolin-14-yl]-N-methyl-2-phenylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-[(2S,4aS,7aR,12aR,14R)-5-(cyclopropylmethyl)-9-hydroxy-2,3,4,4a,5,6,7,12-octahydro-1H-2,7a-ethanoindeno[1,2-d]quinolin-14-yl]-N-methyl-2-phenylacetamide
• 英文别名: N-[(1R,9R,11R,14S,19R)-15-(cyclopropylmethyl)-4-hydroxy-15-azapentacyclo[9.6.2.01,9.02,7.09,14]nonadeca-2(7),3,5-trien-19-yl]-N-methyl-2-phenylacetamide
• 化学式: C₃₁H₃₈N₂O₂
• 分子量: 470.655
• InChiKey: CLPXFKZSJJMNEE-CHICSTKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2S,4aS,7aR,12aR)-5-(cyclopropylmethyl)-9-methoxy-2,4a,5,6,7,12-hexahydro-1H-2,7a-ethanoindeno[1,2-d]quinolin-14-one 在 palladium 10% on activated carbon 、 氢气 、 吡啶盐酸盐 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 39.5h， 生成 N-[(2S,4aS,7aR,12aR,14R)-5-(cyclopropylmethyl)-9-hydroxy-2,3,4,4a,5,6,7,12-octahydro-1H-2,7a-ethanoindeno[1,2-d]quinolin-14-yl]-N-methyl-2-phenylacetamide
  参考文献：
  名称：

  Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain

  摘要：

  We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a beta-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.036

文献信息

• Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain
  作者：Ryo Nakajima、Naoshi Yamamoto、Shigeto Hirayama、Takashi Iwai、Akiyoshi Saitoh、Yasuyuki Nagumo、Hideaki Fujii、Hiroshi Nagase

  DOI：10.1016/j.bmc.2015.08.036

  日期：2015.10

  We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a beta-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine. (C) 2015 Elsevier Ltd. All rights reserved.