tert-butyl 4-(2-(methyl(phenyl)amino)-2-oxoethyl)piperazine-1-carboxylate | 1452806-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(2-(methyl(phenyl)amino)-2-oxoethyl)piperazine-1-carboxylate
• CAS: 1452806-98-2
• 化学式: C₁₈H₂₇N₃O₃
• 分子量: 333.431
• InChiKey: QRBFGHSTZSXJBR-UHFFFAOYSA-N

物化性质

• 沸点：
  440.8±40.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  53.09
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(methyl(phenyl)amino)-2-oxoethyl)piperazine-1-carboxylate 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 24.0h， 生成 2-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-N-methyl-N-phenylacetamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolebutylamines as a Novel Class of Selective Dopamine D3 Receptor Ligands

  摘要：

  A series of indolebutylamine derivatives were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine 3 receptor. The most potent compound 11q binds to dopamine 3 receptor with a Ki value of 124 nm and displays excellent selectivity over the dopamine 1 receptor and dopamine 2 receptor. Investigation based on structural information indicates that site S182 located in extracellular loop 2 may account for high selectivity of compounds. Interaction models of the dopamine 3 receptor‐11q complex and structure‐activity relationships were discussed by integrating all available experimental and computational data with the eventual aim to discover potent and selective ligands to dopamine 3 receptor.

  DOI：

  10.1111/cbdd.12158
• 作为产物：
  描述：

  苯胺 在 水 、 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 tert-butyl 4-(2-(methyl(phenyl)amino)-2-oxoethyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Higher-Affinity Agonists of 5-HT_1AR Discovered through Tuning the Binding-Site Flexibility

  摘要：

  Discovery of high-affinity and high-selectivity agonists of 5-HT1AR. has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR-related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (K-i = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agornst-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with,similar to 50-fold increase in receptor-binding affinity and similar to 25-fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D-1, D-2, and D-3).

  DOI：

  10.1021/acs.jcim.5b00164