4-((N-ethyl-4-phenylquinazoline-2-carboxamido)methyl)-phenyl 4-methylbenzenesulfonate | 1581275-72-0

• 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-ethyl-4-phenylquinazoline-2-carboxamido)methyl)-phenyl 4-methylbenzenesulfonate
• CAS: 1581275-72-0
• 化学式: C₃₁H₂₇N₃O₄S
• 分子量: 537.639
• InChiKey: RXPJTYLOMSUJNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.04
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  89.46
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-((N-ethyl-4-phenylquinazoline-2-carboxamido)methyl)-phenyl 4-methylbenzenesulfonate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以96%的产率得到N-ethyl-N-(4-hydroxybenzyl)-4-phenylquinazoline-2-carboxamide
  参考文献：
  名称：

  Structure–Activity Relationship Refinement and Further Assessment of 4-Phenylquinazoline-2-carboxamide Translocator Protein Ligands as Antiproliferative Agents in Human Glioblastoma Tumors

  摘要：

  Structure-activity relationships (SARs) within the 4-phenylquinazoline-2-carboxamide series of translocator protein (TSPO) ligands have been explored further by the synthesis and TSPO binding affinity evaluation of N-benzyl-N-ethyl/methyl derivatives variously decorated at the 6-, 2'-, 4'-, and 4″-positions. Most of the compounds showed high affinity with K(i) values in the nanomolar/subnanomolar range. A pharmacophore model was developed and employed to better address SAR data presented by the new TSPO ligands. A subset of the new compounds (5, 8, 12, and 19) were tested for their ability to inhibit the viability of human glioblastoma cell line U343. The observed antiproliferative effect was demonstrated to be specific for compound 19, endowed with the best combination of binding affinity and efficacy. Furthermore, the ability of 19 to induce mitochondrial membrane dissipation (Δψ(m)) substantiated the intracellular pro-apoptotic mechanism activated by the binding of this class of ligands to TSPO.

  DOI：

  10.1021/jm401721h
• 作为产物：
  描述：

  1,2-二氢-4-苯基喹唑啉-2-羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 4-((N-ethyl-4-phenylquinazoline-2-carboxamido)methyl)-phenyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Structure–Activity Relationship Refinement and Further Assessment of 4-Phenylquinazoline-2-carboxamide Translocator Protein Ligands as Antiproliferative Agents in Human Glioblastoma Tumors

  摘要：

  Structure-activity relationships (SARs) within the 4-phenylquinazoline-2-carboxamide series of translocator protein (TSPO) ligands have been explored further by the synthesis and TSPO binding affinity evaluation of N-benzyl-N-ethyl/methyl derivatives variously decorated at the 6-, 2'-, 4'-, and 4″-positions. Most of the compounds showed high affinity with K(i) values in the nanomolar/subnanomolar range. A pharmacophore model was developed and employed to better address SAR data presented by the new TSPO ligands. A subset of the new compounds (5, 8, 12, and 19) were tested for their ability to inhibit the viability of human glioblastoma cell line U343. The observed antiproliferative effect was demonstrated to be specific for compound 19, endowed with the best combination of binding affinity and efficacy. Furthermore, the ability of 19 to induce mitochondrial membrane dissipation (Δψ(m)) substantiated the intracellular pro-apoptotic mechanism activated by the binding of this class of ligands to TSPO.

  DOI：

  10.1021/jm401721h

文献信息

• Exploiting the 4-Phenylquinazoline Scaffold for the Development of High Affinity Fluorescent Probes for the Translocator Protein (TSPO)
  作者：Ciro Milite、Elisabetta Barresi、Eleonora Da Pozzo、Barbara Costa、Monica Viviano、Amalia Porta、Anna Messere、Gianluca Sbardella、Federico Da Settimo、Ettore Novellino、Sandro Cosconati、Sabrina Castellano、Sabrina Taliani、Claudia Martini

  DOI：10.1021/acs.jmedchem.7b01031

  日期：2017.9.28

  The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an “in-house” collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, despite their molecular extension, these ligands are still easily lodged in the TSPO

  利用喹唑啉类来寻找一种新的易位蛋白（TSPO）荧光探针，该探针具有改善的亲和力和停留时间（RT）。对喹唑啉衍生物“内部”集合的计算研究表明，酰胺氮上具有高度空间要求的基团，尽管它们具有分子延伸性，但这些配体仍很容易沉积在TSPO结合位点。结合分析支持了这一假设，突出了这些配体的纳摩尔/亚纳摩尔亲和力低，以及代表性化合物11的RT较高关于我们先前报道的基于吲哚的荧光探针。由于酰胺氮原子可以被庞大的基团取代，我们通过在此位置进行荧光标记来开发基于喹唑啉的成像工具。确定了具有相关TSPO亲和力，良好的光谱特性和改进的RT的探针。荧光显微镜的结果表明，这些探针在U343细胞系的线粒体水平上特异性标记了TSPO。