4-((2-phenylquinazolin-4-ylamino)methyl)benzoic acid | 1310685-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-((2-phenylquinazolin-4-ylamino)methyl)benzoic acid
• 英文别名: 4-[[(2-Phenylquinazolin-4-yl)amino]methyl]benzoic acid
• CAS: 1310685-44-9
• 化学式: C₂₂H₁₇N₃O₂
• 分子量: 355.396
• InChiKey: SSCJPUNUMQLVEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  75.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-benzyl-2-(piperazin-1-yl)pyrimidine 、 4-((2-phenylquinazolin-4-ylamino)methyl)benzoic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以10%的产率得到(4-(5-benzylpyrimidin-2-yl)piperazin-1-yl)(4-((2-phenylquinazolin-4-ylamino)methyl)phenyl)methanone
  参考文献：
  名称：

  Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives

  摘要：

  Protein kinases play several pertinent roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy toward controlling different malignancies. Despite the great discovery stories during the last two decades, there is still a demand for anticancer small molecules with the potential of being selective on both the protein kinase and/or the cellular level. A series of novel piperazinylpyrimidine compounds were synthesized and tested for their potential to selectively inhibit the growth of certain tumor cell lines included within the NCI-60 cell line panel. MDA-MB-468, a triple-negative/basal-like breast carcinoma, cell line was among the most sensitive cell lines towards compounds 4 and 15. The three most interesting compounds identified in cellular screens (4, 15, and 16) were subjected to kinase profiling and found to have an interesting selective tendency to target certain kinase subfamily members; PDGFR, CK1, RAF and others. Compound 4 showed a selective tendency to bind to and/or inhibit the function of certain KIT and PDGFRA mutants compared to their wild-type isoforms. Piperazinylpyrimidine based derivatives represent a new class of selective kinase inhibitors. Significantly 4 is more potent at inhibiting oncogenic mutant forms of PDGFR family kinases, which is relevant in terms of its potential use in treating tumors that have become resistant to treatment or driven by such mutations. The clinical demand for agents useful in the control of triple-negative/basal-like breast cancer justifies our interest in compound 15 which is a potent growth inhibitor of MDA-MB-468 cell line. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.057
• 作为产物：
  描述：

  4-氨甲基苯甲酸 、 4-氯-2-苯基喹唑啉 在 三乙胺 作用下， 以 异丙醇 为溶剂， 以37%的产率得到4-((2-phenylquinazolin-4-ylamino)methyl)benzoic acid
  参考文献：
  名称：

  Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives

  摘要：

  Protein kinases play several pertinent roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy toward controlling different malignancies. Despite the great discovery stories during the last two decades, there is still a demand for anticancer small molecules with the potential of being selective on both the protein kinase and/or the cellular level. A series of novel piperazinylpyrimidine compounds were synthesized and tested for their potential to selectively inhibit the growth of certain tumor cell lines included within the NCI-60 cell line panel. MDA-MB-468, a triple-negative/basal-like breast carcinoma, cell line was among the most sensitive cell lines towards compounds 4 and 15. The three most interesting compounds identified in cellular screens (4, 15, and 16) were subjected to kinase profiling and found to have an interesting selective tendency to target certain kinase subfamily members; PDGFR, CK1, RAF and others. Compound 4 showed a selective tendency to bind to and/or inhibit the function of certain KIT and PDGFRA mutants compared to their wild-type isoforms. Piperazinylpyrimidine based derivatives represent a new class of selective kinase inhibitors. Significantly 4 is more potent at inhibiting oncogenic mutant forms of PDGFR family kinases, which is relevant in terms of its potential use in treating tumors that have become resistant to treatment or driven by such mutations. The clinical demand for agents useful in the control of triple-negative/basal-like breast cancer justifies our interest in compound 15 which is a potent growth inhibitor of MDA-MB-468 cell line. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.057

文献信息

• Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives
  作者：Hassan M. Shallal、Wade A. Russu

  DOI：10.1016/j.ejmech.2011.02.057

  日期：2011.6

  Protein kinases play several pertinent roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy toward controlling different malignancies. Despite the great discovery stories during the last two decades, there is still a demand for anticancer small molecules with the potential of being selective on both the protein kinase and/or the cellular level. A series of novel piperazinylpyrimidine compounds were synthesized and tested for their potential to selectively inhibit the growth of certain tumor cell lines included within the NCI-60 cell line panel. MDA-MB-468, a triple-negative/basal-like breast carcinoma, cell line was among the most sensitive cell lines towards compounds 4 and 15. The three most interesting compounds identified in cellular screens (4, 15, and 16) were subjected to kinase profiling and found to have an interesting selective tendency to target certain kinase subfamily members; PDGFR, CK1, RAF and others. Compound 4 showed a selective tendency to bind to and/or inhibit the function of certain KIT and PDGFRA mutants compared to their wild-type isoforms. Piperazinylpyrimidine based derivatives represent a new class of selective kinase inhibitors. Significantly 4 is more potent at inhibiting oncogenic mutant forms of PDGFR family kinases, which is relevant in terms of its potential use in treating tumors that have become resistant to treatment or driven by such mutations. The clinical demand for agents useful in the control of triple-negative/basal-like breast cancer justifies our interest in compound 15 which is a potent growth inhibitor of MDA-MB-468 cell line. (C) 2011 Elsevier Masson SAS. All rights reserved.