7-(2-ethoxynaphthalen-1-yl)-6-methylquinazoline-2,4-diamine | 1335223-02-3

• 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: 7-(2-ethoxynaphthalen-1-yl)-6-methylquinazoline-2,4-diamine
• CAS: 1335223-02-3
• 化学式: C₂₁H₂₀N₄O
• 分子量: 344.416
• InChiKey: DYQBRXOQGFCHCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-溴-2-氟-5-甲基苯甲腈 、 2-乙氧基-1-萘硼酸 在 potassium carbonate 、 钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-(2-ethoxynaphthalen-1-yl)-6-methylquinazoline-2,4-diamine
  参考文献：
  名称：

  Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines

  摘要：

  Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim(TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.059

文献信息

• [EN] DIHYDROFOLATE REDUCTASE INHIBITORS<br/>[FR] INHIBITEURS DE LA DIHYDROFOLATE RÉDUCTASE
  申请人：TRIUS THERAPEUTICS

  公开号：WO2011153310A1

  公开（公告）日：2011-12-08

  The present disclosure provides compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, wherein R5, R6 and Z are as described herein. The disclosure also provides pharmaceutical compositions thereof; and methods for inhibiting DHFR activity; and methods for treating cell proliferative diseases, autoimmune disease, inflammatory disease or bacterial, fungal or parasitic infection by administering a compound of Formula I.

  本公开提供式I的化合物：（I）或其药学上可接受的盐，其中R5，R6和Z如本文所述。该公开还提供其药物组成物；以及通过给予式I的化合物来抑制DHFR活性的方法；以及治疗细胞增殖性疾病、自身免疫疾病、炎症性疾病或细菌、真菌或寄生虫感染的方法。
• DIHYDROFOLATE REDUCTASE INHIBITORS
  申请人：Chen Zhiyong

  公开号：US20120136014A1

  公开（公告）日：2012-05-31

  The present disclosure provides compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein R 5 , R 6 and Z are as described herein. The disclosure also provides pharmaceutical compositions thereof; and methods for inhibiting DHFR activity; and methods for treating cell proliferative diseases, autoimmune disease, inflammatory disease or bacterial, fungal or parasitic infection by administering a compound of Formula I.

  本公开提供公式I的化合物：或其药学上可接受的盐，其中R5，R6和Z如本文所述。本公开还提供其制药组合物；以及通过给予公式I的化合物来抑制DHFR活性的方法；以及通过给予公式I的化合物来治疗细胞增殖性疾病，自身免疫性疾病，炎症性疾病或细菌，真菌或寄生虫感染的方法。
• US8835445B2
  申请人：——

  公开号：US8835445B2

  公开（公告）日：2014-09-16
• Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines
  作者：Xiaoming Li、Mark Hilgers、Mark Cunningham、Zhiyong Chen、Michael Trzoss、Junhu Zhang、Lucy Kohnen、Thanh Lam、Chris Creighton、Kedar GC、Kirk Nelson、Bryan Kwan、Mark Stidham、Vickie Brown-Driver、Karen J. Shaw、John Finn

  DOI：10.1016/j.bmcl.2011.07.059

  日期：2011.9

  Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim(TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. (C) 2011 Elsevier Ltd. All rights reserved.