N-ethyl-N-(4-methylbenzyl)-4-phenylquinazoline-2-carboxamide | 1581275-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-ethyl-N-(4-methylbenzyl)-4-phenylquinazoline-2-carboxamide
• 英文别名: N-ethyl-N-[(4-methylphenyl)methyl]-4-phenylquinazoline-2-carboxamide
• CAS: 1581275-45-7
• 化学式: C₂₅H₂₃N₃O
• 分子量: 381.477
• InChiKey: XMDAILZWQZEYJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-phenylquinazoline-2-carboxylic acid 在 氯化亚砜 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 N-ethyl-N-(4-methylbenzyl)-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

文献信息

• Structure–Activity Relationship Refinement and Further Assessment of 4-Phenylquinazoline-2-carboxamide Translocator Protein Ligands as Antiproliferative Agents in Human Glioblastoma Tumors
  作者：Sabrina Castellano、Sabrina Taliani、Monica Viviano、Ciro Milite、Eleonora Da Pozzo、Barbara Costa、Elisabetta Barresi、Agostino Bruno、Sandro Cosconati、Luciana Marinelli、Giovanni Greco、Ettore Novellino、Gianluca Sbardella、Federico Da Settimo、Claudia Martini

  DOI：10.1021/jm401721h

  日期：2014.3.27

  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.