tert-butyl (5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)carbamate | 1610591-82-6

• 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 (5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)carbamate
• 英文别名: tert-butyl N-[5-[4-(2,3-dichlorophenyl)piperazin-1-yl]pentyl]carbamate
• CAS: 1610591-82-6
• 化学式: C₂₀H₃₁Cl₂N₃O₂
• 分子量: 416.391
• InChiKey: RGAGEHAXWCECRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)carbamate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-(5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)-1,1-dimethylurea
  参考文献：
  名称：

  D₂ Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine

  摘要：

  Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both G(i/o)-biased and beta-arrestin2-biased D-2 receptor agonists based on the Food and Drug Administration (FDA)-approved drug aripiprazole. In this work, based on another FDA-approved drug, cariprazine, we conducted a structure-functional selectivity relationship study and discovered compound 38 (MS1768) as a potent partial agonist that selectively activates the G(i/o) pathway over beta-arrestin2. Unlike the dual D2R/D3R partial agonist cariprazine, compound 38 showed selective agonist activity for D2R over D3R. In fact, compound 38 exhibited potent antagonism of dopamine-stimulated beta-arrestin2 recruitment. In our docking studies, compound 38 directly interacts with S193(5.42) on TM5 but has no interactions with extracellular loop 2, which appears to be in contrast to the binding poses of D2R beta-arrestin2-biased ligands. In in vivo studies, compound 38 showed high D2R receptor occupancy in mice and effectively inhibited phencyclidine-induced hyperlocomotion.

  DOI：

  10.1021/acs.jmedchem.9b00508
• 作为产物：
  描述：

  5-(N-叔丁氧羰基氨基)-1-戊醇 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 19.0h， 生成 tert-butyl (5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)carbamate
  参考文献：
  名称：

  Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor

  摘要：

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.

  DOI：

  10.1021/jm500457x