1-[(4aRS,5SR,8aRS)-4-benzyl-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl]-2-phenylethan-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[(4aRS,5SR,8aRS)-4-benzyl-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl]-2-phenylethan-1-one
• 英文别名: 1-[(4aR,8S,8aR)-4-benzyl-8-pyrrolidin-1-yl-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-2-phenylethanone
• 化学式: C₂₇H₃₅N₃O
• 分子量: 417.594
• InChiKey: FTILCKRWMSJYSB-ZWEKWIFMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  26.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(4aRS,5SR,8aRS)-4-benzyl-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl]-2-phenylethan-1-one 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以90%的产率得到2-phenyl-1-[(4aRS,5SR,8aSR)-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl]ethan-1-one
  参考文献：
  名称：

  Combination of cyclohexane and piperazine based κ-opioid receptor agonists: Synthesis and pharmacological evaluation of trans,trans-configured perhydroquinoxalines

  摘要：

  Desymmetrization of the pseudochiral (2r)-configured cyclohexane-1,2,3-triamines 8 with dimethyl oxalate led to racemic aminoquinoxaline-2,3-diones 9. Selective introduction of the kappa pharmacophoric structural elements pyrrolidine and 3,4-dichlorophenylacetamide with a two-carbon distance afforded conformationally restricted kappa agonists 13-15 based on the quinoxaline ring system. In competitive radioligand receptor binding studies the benzylamine 13b, the secondary amine 14b, and the carbamate 15 displayed high kappa receptor affinity. The K-1 value of the lead compound derived methoxycarbonyl derivative 15 is 9.7 nM. However, the x affinity of 15 is exceeded by 13b and 14b with a basic functional group instead of the methoxycarbonyl group in 1-position of the quinoxaline system. The chlorine atoms of the dichlorophenylacetyl residue are essential, since the corresponding phenylacetyl analogs show considerably reduced x affinity. The potent kappa ligands 13b, 14b and 15 are selective over the related mu- and delta-opioid receptors, sigma(1), sigma(2) and NMDA receptors. In the [S-35]GTP gamma S-binding assay 13b behaved as partial agonist with lower activity than U-69,593. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.054
• 作为产物：
  描述：

  (trans,trans)-N1,N3-dibenzyl-2-nitrocyclohexane-1,3-diamine 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 palladium on activated charcoal 、 氢气 、 甲酸铵 、 碳酸氢钠 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 48.08h， 生成 1-[(4aRS,5SR,8aRS)-4-benzyl-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl]-2-phenylethan-1-one
  参考文献：
  名称：

  Combination of cyclohexane and piperazine based κ-opioid receptor agonists: Synthesis and pharmacological evaluation of trans,trans-configured perhydroquinoxalines

  摘要：

  Desymmetrization of the pseudochiral (2r)-configured cyclohexane-1,2,3-triamines 8 with dimethyl oxalate led to racemic aminoquinoxaline-2,3-diones 9. Selective introduction of the kappa pharmacophoric structural elements pyrrolidine and 3,4-dichlorophenylacetamide with a two-carbon distance afforded conformationally restricted kappa agonists 13-15 based on the quinoxaline ring system. In competitive radioligand receptor binding studies the benzylamine 13b, the secondary amine 14b, and the carbamate 15 displayed high kappa receptor affinity. The K-1 value of the lead compound derived methoxycarbonyl derivative 15 is 9.7 nM. However, the x affinity of 15 is exceeded by 13b and 14b with a basic functional group instead of the methoxycarbonyl group in 1-position of the quinoxaline system. The chlorine atoms of the dichlorophenylacetyl residue are essential, since the corresponding phenylacetyl analogs show considerably reduced x affinity. The potent kappa ligands 13b, 14b and 15 are selective over the related mu- and delta-opioid receptors, sigma(1), sigma(2) and NMDA receptors. In the [S-35]GTP gamma S-binding assay 13b behaved as partial agonist with lower activity than U-69,593. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.054