4-(benzylamino)-2-chloro-6-methoxyquinazoline

• 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-(benzylamino)-2-chloro-6-methoxyquinazoline
• 英文别名: N-benzyl-2-chloro-6-methoxyquinazolin-4-amine
• 化学式: C₁₆H₁₄ClN₃O
• 分子量: 299.76
• InChiKey: GXNKEXNZESBWFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  咪唑 、 4-(benzylamino)-2-chloro-6-methoxyquinazoline 在 苯酚 作用下， 反应 0.33h， 以79%的产率得到4-(benzylamino)-2-(imidazol-1-yl)-6-methoxyquinazoline
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014
• 作为产物：
  描述：

  5-甲氧基喹唑啉-(2,4)二酮 在 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 反应 69.0h， 生成 4-(benzylamino)-2-chloro-6-methoxyquinazoline
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014

文献信息

• Characterizing the Antimicrobial Activity of <i>N</i> ² , <i>N</i> ⁴ -Disubstituted Quinazoline-2,4-Diamines toward Multidrug-Resistant Acinetobacter baumannii
  作者：Renee Fleeman、Kurt S. Van Horn、Megan M. Barber、Whittney N. Burda、David L. Flanigan、Roman Manetsch、Lindsey N. Shaw

  DOI：10.1128/aac.00059-17

  日期：2017.6

  dihydrofolate reductase inhibitors with potent in vitro and in vivo antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. In this work, we extended our previous study to the Gram-negative pathogen Acinetobacter baumannii We determined that optimized N2,N4-disubstituted quinazoline-2,4-diamines are strongly antibacterial against multidrug-resistant A. baumannii strains

  我们以前报道了一系列N2，N4-二取代的喹唑啉-2,4-二胺作为二氢叶酸还原酶抑制剂，对耐甲氧西林的金黄色葡萄球菌（MRSA）菌株具有有效的体外和体内抗菌活性。在这项工作中，我们将先前的研究扩展到革兰氏阴性病原鲍曼不动杆菌。我们确定，当6位为9位时，经优化的N2，N4-二取代喹唑啉-2,4-二胺对多药耐药鲍曼不动杆菌菌株具有较强的抗菌作用。被卤化物或烷基取代基取代。此类药物显示出强大的抗菌活性，MIC低至0.5μM，同时被证明具有强力杀菌作用。有趣的是，这些化合物还具有抗生物膜活性的潜力，可消除MIC处或附近的生物膜中90％的细胞。使用连续传代测定，与现有的叶酸合成抑制剂（如甲氧苄氨嘧啶（增加64倍）和磺胺甲恶唑（增加128倍））相比，我们观察到对这些分子产生抗药性的能力有限（MIC增加4倍）。我们还确定了对人细胞的有限毒性，第4和第5号先导剂的50％致死剂量（LD50s）≤23μM。最后
• N2N N4-disubstituted quinazoline-2,4-diamines and uses thereof
  申请人：Manetsch Roman

  公开号：US10323007B1

  公开（公告）日：2019-06-18

  Described herein are quinazoline-based compounds and formulations thereof. In some embodiments, the compounds and/or formulations thereof can be effective to inhibit and/or kill A. baumannii. Also described herein are methods of treating a subject in need thereof by administering to the subject in need thereof a quinazoline-based compound and/or formulation thereof to the subject in need thereof.

  本文描述了基于喹唑啉的化合物及其配方。在某些实施例中，这些化合物和/或其配方可有效抑制和/或杀灭鲍曼氏不动杆菌。本文还描述了通过向需要治疗的受试者投与基于喹唑啉的化合物和/或其配方来治疗需要的受试者的方法。