N-(4-phenylquinazolin-2-yl)benzamide | 575461-58-4

• 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-(4-phenylquinazolin-2-yl)benzamide
• CAS: 575461-58-4
• 化学式: C₂₁H₁₅N₃O
• mdl: MFCD03871879
• 分子量: 325.37
• InChiKey: NSFAASDEMCDBNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-苯基喹唑啉-2-胺 、 alkaline earth salt of/the/ methylsulfuric acid 在 copper(l) iodide 、 potassium carbonate 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 作用下， 以 甲苯 为溶剂， 生成 N-(4-phenylquinazolin-2-yl)benzamide
  参考文献：
  名称：

  Development of inhibitors of heterotrimeric Gαi subunits

  摘要：

  Heterotrimeric G-proteins are the immediate downstream effectors of G-protein coupled receptors (GPCRs). Endogenous protein guanine nucleotide dissociation inhibitors (GDIs) like AGS3/4 and RGS12/14 function through GPR/Goloco GDI domains. Extensive characterization of GPR domain peptides indicate they function as selective GDIs for G alpha(i) by competing for the GPCR and G beta gamma and preventing GDP release. We modified a GPR consensus peptide by testing FGF and TAT leader sequences to make the peptide cell permeable. FGF modification inhibited GDI activity while TAT preserved GDI activity. TAT-GPR suppresses G-protein coupling to the receptor and completely blocked alpha(2)-adrenoceptor (alpha(2)AR) mediated decreases in cAMP in HEK293 cells at 100 nM. We then sought to discover selective small molecule inhibitors for G alpha(i). Molecular docking was used to identify potential molecules that bind to and stabilize the G alpha(i)-GDP complex by directly interacting with both G alpha(i) and GDP. G alpha(i)-GTP and G alpha(q)-GDP were used as a computational counter screen and G alpha(q)-GDP was used as a biological counter screen. Thirty-seven molecules were tested using nucleotide exchange. STD NMR assays with compound 0990, a quinazoline derivative, showed direct interaction with G alpha(i). Several compounds showed G alpha(1) specific inhibition and were able to block alpha(2)AR mediated regulation of cAMP. In addition to being a pharmacologic tool, GDI inhibition of G alpha subunits has the advantage of circumventing the upstream component of GPCR-related signaling in cases of over-stimulation by agonists, mutations, polymorphisms, and expression-related defects often seen in disease. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.035