tert-butyl 2-(((3,4-difluorophenyl)amino)methyl)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 2-(((3,4-difluorophenyl)amino)methyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 2-[(3,4-difluoroanilino)methyl]piperidine-1-carboxylate；tert-butyl 2-[(3,4-difluoroanilino)methyl]piperidine-1-carboxylate
• 化学式: C₁₇H₂₄F₂N₂O₂
• 分子量: 326.387
• InChiKey: FOMRTJIBHUSJDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(((3,4-difluorophenyl)amino)methyl)piperidine-1-carboxylate 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 10.0h， 生成 N-(3,4-difluorophenyl)-N-((1-(((5S)-5-((tetrahydro-2H-pyran-2-yl)oxy)-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)piperidin-2-yl)methyl)propionamide
  参考文献：
  名称：

  Design synthesis and structure–activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands

  摘要：

  Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl) methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the mu opioid receptor over the delta opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the mu opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75 +/- 21 nM, and 190 +/- 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170 +/- 42 nM, in contrast to its binding affinity results. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.030
• 作为产物：
  描述：

  1-BOC-2-哌啶甲醛 、 3,4-二氟苯胺 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以81%的产率得到tert-butyl 2-(((3,4-difluorophenyl)amino)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design synthesis and structure–activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands

  摘要：

  Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl) methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the mu opioid receptor over the delta opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the mu opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75 +/- 21 nM, and 190 +/- 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170 +/- 42 nM, in contrast to its binding affinity results. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.030

文献信息

• Design synthesis and structure–activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands
  作者：Srinivas Deekonda、David Rankin、Peg Davis、Josephine Lai、Todd. W. Vanderah、Frank Porecca、Victor J. Hruby

  DOI：10.1016/j.bmc.2015.11.030

  日期：2016.1

  Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl) methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the mu opioid receptor over the delta opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the mu opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75 +/- 21 nM, and 190 +/- 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170 +/- 42 nM, in contrast to its binding affinity results. (C) 2015 Elsevier Ltd. All rights reserved.