4-[[N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl]aminocyclohex-1-en-1-yl] trifluoromethane sulfonate | 1072881-00-5

• 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: 4-[[N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl]aminocyclohex-1-en-1-yl] trifluoromethane sulfonate
• 英文别名: [4-[4-[4-(4-Phenylphenyl)triazol-1-yl]butyl-propylamino]cyclohexen-1-yl] trifluoromethanesulfonate
• CAS: 1072881-00-5
• 化学式: C₂₈H₃₃F₃N₄O₃S
• 分子量: 562.656
• InChiKey: OFWFCWRHDZBBHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  85.7
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-[[N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl]aminocyclohex-1-en-1-yl] trifluoromethane sulfonate 、 三甲基乙炔基硅 在 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 二甲基十二/十四烷基叔胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以6.6 mg的产率得到N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl-N-[4-(2-trimethylsilylethynyl)cyclohex-3-en-1-yl]amine
  参考文献：
  名称：

  Novel D3 Selective Dopaminergics Incorporating Enyne Units as Nonaromatic Catechol Bioisosteres: Synthesis, Bioactivity, and Mutagenesis Studies

  摘要：

  Enynes of type 4 and 5 as long chain derivatives of the nonaromatic dopamine D-3 receptor agonist 3 (FAUC 73) were prepared by exploiting chemoselective functionalization of the azido-substituted vinyl triflate 9. Radioligand binding Studies indicated excellent D-3 affinity and selectivity over related GPCRs for the terminal alkynes 4c (FAUC 460) and 5c. Biphasic displacement Curves gave picomolar K-i values for the high affinity binding site of D-3. According to mitogenesis experiments and bioluminescence based cAMP assays, the biphenylcarboxamide 4c and its click chemistry derived triazole analogue 5c behaved as strong partial agonists but relative ligand efficacy significantly depended on the type of functional assay. Site directed mutagenesis involving the mutants D-3 D3.32E, and D-3 F6.51W implied that ligand interactions with D3.32 and F6.51 are highly crucial. giving rise to analogous binding modes for dopamine, classical and enyne type agonists.

  DOI：

  10.1021/jm800895v
• 作为产物：
  描述：

  三氟甲磺酸酐 、 4-[N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl]aminocyclohexan-1-one 在 2,6-二叔丁基-4-甲基吡啶 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 15.0h， 生成 4-[[N-[4-[4-(4-biphenyl)triazol-1-yl]butyl]-N-propyl]aminocyclohex-1-en-1-yl] trifluoromethane sulfonate
  参考文献：
  名称：

  Novel D3 Selective Dopaminergics Incorporating Enyne Units as Nonaromatic Catechol Bioisosteres: Synthesis, Bioactivity, and Mutagenesis Studies

  摘要：

  Enynes of type 4 and 5 as long chain derivatives of the nonaromatic dopamine D-3 receptor agonist 3 (FAUC 73) were prepared by exploiting chemoselective functionalization of the azido-substituted vinyl triflate 9. Radioligand binding Studies indicated excellent D-3 affinity and selectivity over related GPCRs for the terminal alkynes 4c (FAUC 460) and 5c. Biphasic displacement Curves gave picomolar K-i values for the high affinity binding site of D-3. According to mitogenesis experiments and bioluminescence based cAMP assays, the biphenylcarboxamide 4c and its click chemistry derived triazole analogue 5c behaved as strong partial agonists but relative ligand efficacy significantly depended on the type of functional assay. Site directed mutagenesis involving the mutants D-3 D3.32E, and D-3 F6.51W implied that ligand interactions with D3.32 and F6.51 are highly crucial. giving rise to analogous binding modes for dopamine, classical and enyne type agonists.

  DOI：

  10.1021/jm800895v

文献信息

• Novel D3 Selective Dopaminergics Incorporating Enyne Units as Nonaromatic Catechol Bioisosteres: Synthesis, Bioactivity, and Mutagenesis Studies
  作者：Miriam Dörfler、Nuska Tschammer、Katharina Hamperl、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm800895v

  日期：2008.11.13

  Enynes of type 4 and 5 as long chain derivatives of the nonaromatic dopamine D-3 receptor agonist 3 (FAUC 73) were prepared by exploiting chemoselective functionalization of the azido-substituted vinyl triflate 9. Radioligand binding Studies indicated excellent D-3 affinity and selectivity over related GPCRs for the terminal alkynes 4c (FAUC 460) and 5c. Biphasic displacement Curves gave picomolar K-i values for the high affinity binding site of D-3. According to mitogenesis experiments and bioluminescence based cAMP assays, the biphenylcarboxamide 4c and its click chemistry derived triazole analogue 5c behaved as strong partial agonists but relative ligand efficacy significantly depended on the type of functional assay. Site directed mutagenesis involving the mutants D-3 D3.32E, and D-3 F6.51W implied that ligand interactions with D3.32 and F6.51 are highly crucial. giving rise to analogous binding modes for dopamine, classical and enyne type agonists.