2-isopropyl-5-(4-(4-(2-methylquinolin-8-yl)piperazin-1-yl)-butoxy)benzo[d]thiazole

• 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: 2-isopropyl-5-(4-(4-(2-methylquinolin-8-yl)piperazin-1-yl)-butoxy)benzo[d]thiazole
• 英文别名: 5-[4-[4-(2-Methylquinolin-8-yl)piperazin-1-yl]butoxy]-2-propan-2-yl-1,3-benzothiazole；5-[4-[4-(2-methylquinolin-8-yl)piperazin-1-yl]butoxy]-2-propan-2-yl-1,3-benzothiazole
• 化学式: C₂₈H₃₄N₄OS
• 分子量: 474.67
• InChiKey: BJICILQUJOQCJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-甲氧基异硫氰酸苯酯 在 氢碘酸 、 potassium carbonate 、 sodium iodide 、 sodium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 乙腈 为溶剂， 反应 22.0h， 生成 2-isopropyl-5-(4-(4-(2-methylquinolin-8-yl)piperazin-1-yl)-butoxy)benzo[d]thiazole
  参考文献：
  名称：

  Discovery of G Protein-Biased D2 Dopamine Receptor Partial Agonists

  摘要：

  Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class,beta-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist. In our continuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold. We designed and synthesized novel analogues to explore two regions of 1 and conducted structure functional selectivity relationship (SFSR) studies. Here we report the discovery of 1, findings from our SFSR studies, and characterization of novel G protein-biased D2R agonists.

  DOI：

  10.1021/acs.jmedchem.6b01208

文献信息

• Discovery of G Protein-Biased D2 Dopamine Receptor Partial Agonists
  作者：Xin Chen、John D. McCorvy、Matthew G. Fischer、Kyle V. Butler、Yudao Shen、Bryan L. Roth、Jian Jin

  DOI：10.1021/acs.jmedchem.6b01208

  日期：2016.12.8

  Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class,beta-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist. In our continuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold. We designed and synthesized novel analogues to explore two regions of 1 and conducted structure functional selectivity relationship (SFSR) studies. Here we report the discovery of 1, findings from our SFSR studies, and characterization of novel G protein-biased D2R agonists.