(4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)(4-aminophenyl)methanone | 90990-95-7

• 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-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)(4-aminophenyl)methanone
• 英文别名: 4-Amino-2-(4-(4-aminobenzoyl)piperazino)-6,7-dimethoxyquinazoline；[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(4-aminophenyl)methanone
• CAS: 90990-95-7
• 化学式: C₂₁H₂₄N₆O₃
• 分子量: 408.46
• InChiKey: UFRKKKXLQITYIE-UHFFFAOYSA-N

物化性质

• 沸点：
  713.8±70.0 °C(Predicted)
• 密度：
  1.348±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  戊二酰基二氯 、 (4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)(4-aminophenyl)methanone 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以70%的产率得到N¹,N⁵-bis(4-(4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazine-1-carbonyl)phenyl)glutaramide
  参考文献：
  名称：

  EphA2 受体的二聚小分子激动剂抑制胶质母细胞瘤细胞的生长。

  摘要：

  EphA2 受体激酶可能成为抗胶质母细胞瘤治疗的新靶点。先前鉴定的多沙唑嗪的作用类似于 EphA2 的内源性配体并诱导细胞凋亡。通过先导结构修饰，具有独特二聚体结构的多沙唑嗪衍生物显示出活性的提高。在目前的研究中，我们通过先导优化扩展了二聚体支架，以探索连接部分的化学空间和核心结构的轻微变化。合成了 27 种新衍生物，并用 EphA2 过表达和野生型胶质母细胞瘤细胞系检查了细胞增殖和 EphA2 活化。三个新化合物3d、3e和7bg显示出针对 EphA2 过表达的胶质母细胞瘤细胞生长的有效和选择性活性。二聚体3d修饰用短聚乙二醇链替换长烷基链。与化合物3d相比，二聚体7bg具有相对较长的聚乙二醇链，并且长度与先导化合物更相似。而二聚体3e具有探索化学空间的刚性芳族接头。活性中接头的多样性表明额外的氢结合位点与活性呈正相关。所有三种二聚体在 EphA2 过表达细胞中均显示出选择性活性，表明该活性与

  DOI：

  10.1016/j.bmc.2020.115656
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 在 盐酸 、 氨 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 叔丁醇 为溶剂， 反应 70.0h， 生成 (4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)(4-aminophenyl)methanone
  参考文献：
  名称：

  A Modified Synthesis of Iodoazidoaryl Prazosin

  摘要：

  The antihypertension agent iodoazidoaryl prazosin (IAAP) has been made using a convergent route involving addition of an acylated piperazine 7 to 2-chloroquinazoline 5. IAAP has been shown to function as a multidrug resistance (MDR) reversal agent and bind to P-glycoprotein, a transmembrane transport protein. A study is also reported involving palladium-catalyzed substitution with amine heterocycles. With N,N-bis(2,6-diisopropyl)dihydroimidazolium chloride (10) as the ligand (2 mol %) for palladium(II) acetate (2 mol %) in THF at room temperature, morpholine added to 5 in 81% yield.

  DOI：

  10.1021/jo026217o

文献信息

• Pharmacological Exploitation of the α1-Adrenoreceptor Antagonist Doxazosin to Develop a Novel Class of Antitumor Agents That Block Intracellular Protein Kinase B/Akt Activation
  作者：Yeng-Jeng Shaw、Ya-Ting Yang、Jason B. Garrison、Natasha Kyprianou、Ching-Shih Chen

  DOI：10.1021/jm049752k

  日期：2004.8.1

  The alpha1-adrenoreceptor antagonist doxazosin induces apoptosis in malignant cells with moderate potency via an alpha1-adrenoreceptor-independent mechanism. Here, we demonstrate that the ability of doxazosin to induce apoptosis in PC-3 prostate cancer cells was, in part, attributable to the inhibition of protein kinase B (PKB)/Akt activation. The separation of the effect of doxazosin on apoptosis from its original pharmacological activity provides molecular underpinnings to develop novel antitumor agents. Replacement of the (2,3-dihydro-benzo[1,4]dioxane)-carbonyl moiety of doxazosin with aryl-sulfonyl functions dramatically improves the potency in facilitating Akt deactivation and inducing apoptosis. The optimal compounds, 33 and 44, were effective in apoptosis induction at low micromolar concentrations irrespective of androgen dependency and p53 functional status. Both agents were active in suppressing the growth of a panel of 60 cancer-cell lines with IC50 values of 2.2 and 1.5 muM, respectively. Together, these in vitro efficacy data suggest the translational potential of these agents in prostate cancer treatment.
• US4440769A
  申请人：——

  公开号：US4440769A

  公开（公告）日：1984-04-03
• A Modified Synthesis of Iodoazidoaryl Prazosin
  作者：Merritt B. Andrus、Sashikumar N. Mettath、Chun Song

  DOI：10.1021/jo026217o

  日期：2002.11.1

  The antihypertension agent iodoazidoaryl prazosin (IAAP) has been made using a convergent route involving addition of an acylated piperazine 7 to 2-chloroquinazoline 5. IAAP has been shown to function as a multidrug resistance (MDR) reversal agent and bind to P-glycoprotein, a transmembrane transport protein. A study is also reported involving palladium-catalyzed substitution with amine heterocycles. With N,N-bis(2,6-diisopropyl)dihydroimidazolium chloride (10) as the ligand (2 mol %) for palladium(II) acetate (2 mol %) in THF at room temperature, morpholine added to 5 in 81% yield.
• Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth
  作者：Cody M. Orahoske、Yaxin Li、Aaron Petty、Fatma M. Salem、Jovana Hanna、Wenjing Zhang、Bin Su、Bingcheng Wang

  DOI：10.1016/j.bmc.2020.115656

  日期：2020.9

  Dimer 7bg has a relatively longer polyethylene glycol chain in comparison to compound 3d and the length is more similar to the lead compound. Whereas dimer 3e has a rigid aromatic linker exploring the chemical space. The diversity of the linkers in the active suggest additional hydrogen binding sites has a positive correlation to the activity. All three dimers showed selective activity in EphA2 overexpressed

  EphA2 受体激酶可能成为抗胶质母细胞瘤治疗的新靶点。先前鉴定的多沙唑嗪的作用类似于 EphA2 的内源性配体并诱导细胞凋亡。通过先导结构修饰，具有独特二聚体结构的多沙唑嗪衍生物显示出活性的提高。在目前的研究中，我们通过先导优化扩展了二聚体支架，以探索连接部分的化学空间和核心结构的轻微变化。合成了 27 种新衍生物，并用 EphA2 过表达和野生型胶质母细胞瘤细胞系检查了细胞增殖和 EphA2 活化。三个新化合物3d、3e和7bg显示出针对 EphA2 过表达的胶质母细胞瘤细胞生长的有效和选择性活性。二聚体3d修饰用短聚乙二醇链替换长烷基链。与化合物3d相比，二聚体7bg具有相对较长的聚乙二醇链，并且长度与先导化合物更相似。而二聚体3e具有探索化学空间的刚性芳族接头。活性中接头的多样性表明额外的氢结合位点与活性呈正相关。所有三种二聚体在 EphA2 过表达细胞中均显示出选择性活性，表明该活性与