6-bromo-N-(pyridin-3-ylmethyl)quinazolin-4-amine | 307538-38-1

• 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: 6-bromo-N-(pyridin-3-ylmethyl)quinazolin-4-amine
• CAS: 307538-38-1
• 化学式: C₁₄H₁₁BrN₄
• 分子量: 315.172
• InChiKey: LOJJSHJKBLDRED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-呋喃硼酸 、 6-bromo-N-(pyridin-3-ylmethyl)quinazolin-4-amine 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 6-(furan-2-yl)-N-(pyridin-3-ylmethyl)quinazolin-4-amine
  参考文献：
  名称：

  Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk)

  摘要：

  A series of substituted 6-arylquinazolin-4-amines were prepared and analyzed as inhibitors of Clk4. Synthesis, structure-activity relationships and the selectivity of a potent analogue against a panel of 402 kinases are presented. Inhibition of Clk4 by these agents at varied concentrations of assay substrates (ATP and receptor peptide) highly suggests that this chemotype is an ATP competitive inhibitor. Molecular docking provides further evidence that inhibition is the result of binding at the kinase hinge region. Selected compounds represent novel tools capable of potent and selective inhibition of Clk1, Clk4, and Dyrk1A. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.09.121
• 作为产物：
  描述：

  3-氨甲基吡啶 、 6-溴-4-氯喹唑啉 在 三乙胺 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 生成 6-bromo-N-(pyridin-3-ylmethyl)quinazolin-4-amine
  参考文献：
  名称：

  Fabrication of Furan-Functionalized Quinazoline Hybrids: Their Antibacterial Evaluation, Quantitative Proteomics, and Induced Phytopathogen Morphological Variation Studies

  摘要：

  The limited number of agrochemicals targeting plant bacterial diseases has driven us to develop highly efficient, low-cost, and versatile antibacterial alternatives. Herein, a novel type of simple furan-functionalized quinazolin-4-amines was systematically fabricated and screened for their antibacterial activity. Bioassay results revealed that compounds C-1 and E-4 could substantially block the growth of two frequently mentioned pathogens Xanthomonas oryzae pv oryzae and X. axonopodis pv citri in vitro, displaying appreciable EC50 values of 7.13 and 10.3 mg/L, respectively. This effect was prominently improved by comparing those of mainly used agrochemicals. An in vivo experiment against bacterial blight further illustrated their viable applications as antimicrobial ingredients. Quantitative proteomics demonstrated that C-1 possessed a remarkable ability to manipulate the upregulation and downregulation of expressed proteins, which probably involved D-glucose and biotin metabolic pathways. This finding was substantially verified by parallel reaction monitoring analysis. Scanning electron microscopy images and fluorescence spectra also indicated that the designed compounds had versatile capacities for destroying the integrity of bacteria. Given these remarkable characteristics, furan-functionalized quinazoline hybrids can serve as a viable platform for developing innovative antibiotic alternatives against bacterial infections.

  DOI：

  10.1021/acs.jafc.9b03419

文献信息

• TARGETING NAD BIOSYNTHESIS IN BACTERIAL PATHOGENS
  申请人：Mackerell, JR. Alexander

  公开号：US20120190708A1

  公开（公告）日：2012-07-26

  The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. To this end, the inventors have identified small molecule compounds that inhibit bacterial target enzymes by interacting with a novel inhibitory binding site on the enzyme while having no effect on functionally equivalent human enzymes.

  多重耐药病原体的出现需要寻找作用于先前未被开发的靶标的新抗生素。Nicotinate单核苷酸腺苷转移酶（NadD家族），是大多数细菌NAD生物合成的必需酶，被选为基于结构的抑制剂开发的目标。为此，发明人已经鉴定出小分子化合物，通过与酶上的新型抑制性结合位点相互作用来抑制细菌靶标酶，而对功能相当的人类酶没有影响。
• US8785499B2
  申请人：——

  公开号：US8785499B2

  公开（公告）日：2014-07-22
• Fabrication of Furan-Functionalized Quinazoline Hybrids: Their Antibacterial Evaluation, Quantitative Proteomics, and Induced Phytopathogen Morphological Variation Studies
  作者：Qing-Su Long、Li-Wei Liu、Yong-Liang Zhao、Pei-Yi Wang、Biao Chen、Zhong Li、Song Yang

  DOI：10.1021/acs.jafc.9b03419

  日期：2019.10.9

  The limited number of agrochemicals targeting plant bacterial diseases has driven us to develop highly efficient, low-cost, and versatile antibacterial alternatives. Herein, a novel type of simple furan-functionalized quinazolin-4-amines was systematically fabricated and screened for their antibacterial activity. Bioassay results revealed that compounds C-1 and E-4 could substantially block the growth of two frequently mentioned pathogens Xanthomonas oryzae pv oryzae and X. axonopodis pv citri in vitro, displaying appreciable EC50 values of 7.13 and 10.3 mg/L, respectively. This effect was prominently improved by comparing those of mainly used agrochemicals. An in vivo experiment against bacterial blight further illustrated their viable applications as antimicrobial ingredients. Quantitative proteomics demonstrated that C-1 possessed a remarkable ability to manipulate the upregulation and downregulation of expressed proteins, which probably involved D-glucose and biotin metabolic pathways. This finding was substantially verified by parallel reaction monitoring analysis. Scanning electron microscopy images and fluorescence spectra also indicated that the designed compounds had versatile capacities for destroying the integrity of bacteria. Given these remarkable characteristics, furan-functionalized quinazoline hybrids can serve as a viable platform for developing innovative antibiotic alternatives against bacterial infections.
• Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk)
  作者：Bryan T. Mott、Cordelle Tanega、Min Shen、David J. Maloney、Paul Shinn、William Leister、Juan J. Marugan、James Inglese、Christopher P. Austin、Tom Misteli、Douglas S. Auld、Craig J. Thomas

  DOI：10.1016/j.bmcl.2009.09.121

  日期：2009.12

  A series of substituted 6-arylquinazolin-4-amines were prepared and analyzed as inhibitors of Clk4. Synthesis, structure-activity relationships and the selectivity of a potent analogue against a panel of 402 kinases are presented. Inhibition of Clk4 by these agents at varied concentrations of assay substrates (ATP and receptor peptide) highly suggests that this chemotype is an ATP competitive inhibitor. Molecular docking provides further evidence that inhibition is the result of binding at the kinase hinge region. Selected compounds represent novel tools capable of potent and selective inhibition of Clk1, Clk4, and Dyrk1A. Published by Elsevier Ltd.