N-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide | 1443990-84-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-[1-(imidazole-1-carbonyl)piperidin-4-yl]-4-methylpyrazole-3-carboxamide
• CAS: 1443990-84-8
• 化学式: C₂₆H₂₃Cl₃N₆O₂
• 分子量: 557.867
• InChiKey: KQBZKSRUMZWTSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  85
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide 、 6α-oxymorphamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到4-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-N-((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Bivalent Ligands That Target μ Opioid (MOP) and Cannabinoid1 (CB₁) Receptors Are Potent Analgesics Devoid of Tolerance

  摘要：

  Given that mu opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both mu agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

  DOI：

  10.1021/jm4005219
• 作为产物：
  描述：

  tert-butyl 4-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-amido]piperidine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 N-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Bivalent Ligands That Target μ Opioid (MOP) and Cannabinoid1 (CB₁) Receptors Are Potent Analgesics Devoid of Tolerance

  摘要：

  Given that mu opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both mu agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

  DOI：

  10.1021/jm4005219

文献信息

• Bivalent Ligands That Target μ Opioid (MOP) and Cannabinoid1 (CB₁) Receptors Are Potent Analgesics Devoid of Tolerance
  作者：Morgan Le Naour、Eyup Akgün、Ajay Yekkirala、Mary M. Lunzer、Mike D. Powers、Alexander E. Kalyuzhny、Philip S. Portoghese

  DOI：10.1021/jm4005219

  日期：2013.7.11

  Given that mu opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both mu agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.