N-(5-chlorobenzoxazol-2-yl)-5-(4-(4-chlorophenyl) piperazin-1-yl)pentanamide

• 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: N-(5-chlorobenzoxazol-2-yl)-5-(4-(4-chlorophenyl) piperazin-1-yl)pentanamide
• 英文别名: N-(5-chloro-1,3-benzoxazol-2-yl)-5-[4-(4-chlorophenyl)piperazin-1-yl]pentanamide
• 化学式: C₂₂H₂₄Cl₂N₄O₂
• 分子量: 447.364
• InChiKey: MTAPPRSTZHJBOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴戊酸乙酯 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N-(5-chlorobenzoxazol-2-yl)-5-(4-(4-chlorophenyl) piperazin-1-yl)pentanamide
  参考文献：
  名称：

  Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein, we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro. Compound 4d was found to be the most potent D3R-selective ligand among these hybrid derivatives. Molecular modeling revealed that extracellular loop 1 (EL1) and loop 2 (EL2) of D3R together likely contribute to D3R selectivity over D2R. In particular, Gly94 in EL1 of D3R may act as a molecular determinant for D3R specificity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.072

文献信息

• Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands
  作者：Yongkai Cao、Suresh Paudel、Xiaowei Zhang、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2015.07.072

  日期：2015.9

  The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein, we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro. Compound 4d was found to be the most potent D3R-selective ligand among these hybrid derivatives. Molecular modeling revealed that extracellular loop 1 (EL1) and loop 2 (EL2) of D3R together likely contribute to D3R selectivity over D2R. In particular, Gly94 in EL1 of D3R may act as a molecular determinant for D3R specificity. (C) 2015 Elsevier Ltd. All rights reserved.