(1S,14R)-23-(cyclopropylmethyl)-11,23-diazahexacyclo[12.7.4.01,14.03,12.05,10.015,20]pentacosa-3,5,7,9,11,15(20),16,18-octaen-17-ol | 1613036-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (1S,14R)-23-(cyclopropylmethyl)-11,23-diazahexacyclo[12.7.4.01,14.03,12.05,10.015,20]pentacosa-3,5,7,9,11,15(20),16,18-octaen-17-ol
• CAS: 1613036-97-7
• 化学式: C₂₇H₂₈N₂O
• 分子量: 396.532
• InChiKey: PXIODNLTTYWACV-KAYWLYCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1S,14R)-23-(cyclopropylmethyl)-17-methoxy-11,23-diazahexacyclo[12.7.4.01,14.03,12.05,10.015,20]pentacosa-3,5,7,9,11,15(20),16,18-octaene 在 吡啶盐酸盐 作用下， 生成 (1S,14R)-23-(cyclopropylmethyl)-11,23-diazahexacyclo[12.7.4.01,14.03,12.05,10.015,20]pentacosa-3,5,7,9,11,15(20),16,18-octaen-17-ol
  参考文献：
  名称：

  Design and synthesis of quinolinopropellane derivatives with selective δ opioid receptor agonism

  摘要：

  Indolopropellane 2 was reported to show almost no binding affinity to the delta opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesis that almost no binding affinity of 2 to the DOR would be derived from its possibly stable bent conformer. To enable the propellane skeleton to adopt an extended conformation which would reasonably interact with the DOR, quinolinopropellanes 3a-d were designed which had an additional pharmacophore, quinoline nitrogen. The calculated binding free energies of ligand-DOR complexes strongly supported our working hypothesis. The synthesized quinolinopropellane 3a was a selective DOR full agonist, confirming our working hypothesis and the results of in silico investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.098

文献信息

• Design and synthesis of quinolinopropellane derivatives with selective δ opioid receptor agonism
  作者：Hiroshi Nagase、Ryo Nakajima、Naoshi Yamamoto、Shigeto Hirayama、Takashi Iwai、Toru Nemoto、Hiroaki Gouda、Shuichi Hirono、Hideaki Fujii

  DOI：10.1016/j.bmcl.2014.04.098

  日期：2014.7

  Indolopropellane 2 was reported to show almost no binding affinity to the delta opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesis that almost no binding affinity of 2 to the DOR would be derived from its possibly stable bent conformer. To enable the propellane skeleton to adopt an extended conformation which would reasonably interact with the DOR, quinolinopropellanes 3a-d were designed which had an additional pharmacophore, quinoline nitrogen. The calculated binding free energies of ligand-DOR complexes strongly supported our working hypothesis. The synthesized quinolinopropellane 3a was a selective DOR full agonist, confirming our working hypothesis and the results of in silico investigation. (C) 2014 Elsevier Ltd. All rights reserved.