(4-(5-benzylpyrimidin-2-yl)piperazin-1-yl)(4-(2-phenylquinazolin-4-ylamino)phenyl)methanone | 1310685-55-2

• 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: (4-(5-benzylpyrimidin-2-yl)piperazin-1-yl)(4-(2-phenylquinazolin-4-ylamino)phenyl)methanone
• 英文别名: (4-(5-benzylpyrimidin-2-yl)piperazin-1-yl)(4-(2-phenylquinazolin-4ylamino)phenyl)methanone；[4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl]-[4-[(2-phenylquinazolin-4-yl)amino]phenyl]methanone
• CAS: 1310685-55-2
• 化学式: C₃₆H₃₁N₇O
• 分子量: 577.688
• InChiKey: LCDRJJLZWJDBNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-2-苯基喹唑啉 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 、 异丙醇 为溶剂， 生成 (4-(5-benzylpyrimidin-2-yl)piperazin-1-yl)(4-(2-phenylquinazolin-4-ylamino)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

文献信息

• PIPERAZINYLPYRIMIDINE ANALOGUES AS PROTEIN KINASE INHIBITORS
  申请人：RUSSU Wade A.

  公开号：US20120053183A1

  公开（公告）日：2012-03-01

  The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same.

  该发明提供了基于哌嗪基嘧啶衍生物的新化合物，用作蛋白激酶抑制剂。这些化合物可能在治疗或预防不同的细胞增殖紊乱疾病，如癌症方面具有用处。本发明还提供了制备这些化合物的方法，以及使用这些化合物的方法。
• US8609672B2
  申请人：——

  公开号：US8609672B2

  公开（公告）日：2013-12-17
• 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.