4-氯-6-(3,4-二甲氧基-苯基)-喹唑啉 | 1005010-01-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-6-(3,4-二甲氧基-苯基)-喹唑啉
• 英文名称: 4-chloro-6-(3,4-dimethoxy-phenyl)-quinazoline
• 英文别名: 4-Chloro-6-(3,4-dimethoxy-phenyl)-quinazoline；4-chloro-6-(3,4-dimethoxyphenyl)quinazoline
• CAS: 1005010-01-4
• 化学式: C₁₆H₁₃ClN₂O₂
• 分子量: 300.744
• InChiKey: BPRVNFDTLDWSLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-6-(3,4-二甲氧基-苯基)-喹唑啉 在 吡啶 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-(6-(3,4-dimethoxyphenyl)quinazolin-4-yl)cyclohexanecarboxamide
  参考文献：
  名称：

  Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach

  摘要：

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.

  DOI：

  10.1021/jm5007929
• 作为产物：
  描述：

  6-溴-4-羟基喹唑啉 在 四(三苯基膦)钯 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 水 为溶剂， 反应 14.0h， 生成 4-氯-6-(3,4-二甲氧基-苯基)-喹唑啉
  参考文献：
  名称：

  Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach

  摘要：

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.

  DOI：

  10.1021/jm5007929

文献信息

• 2,4-Substituted Quinazolines as Lipid Kinase Inhibitors
  申请人：Stauffer Frederic

  公开号：US20090258882A1

  公开（公告）日：2009-10-15

  The invention relates to compounds of the formula I, which are appropriate for the treatment of kinase, e.g. PI3K-related, diseases, such as proliferative diseases, inflammatory diseases, obstructive airways disorders and transplantation related diseases.

  该发明涉及式I的化合物，适用于治疗激酶，例如PI3K相关的疾病，如增殖性疾病、炎症性疾病、阻塞性呼吸道疾病和移植相关疾病。
• 4,6-DI- AND 2,4,6-TRISUBSTITUTED QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING VIRAL INFECTIONS
  申请人：Gao Ling-Jie

  公开号：US20100143299A1

  公开（公告）日：2010-06-10

  This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R 2 is selected from the group consisting of hydrogen, NR′R″ and C 1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O) n , C 1-7 alkylene, C 2-7 alkenylene and C 2-7 alkynylene; R 4 is selected from the group consisting of C 1-7 alkyl, C 2-7 alkenyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C 1-7 alkylene, C 2-7 alkenylene, and C 2-7 alkynylene; n is 0, 1 or 2; and R 6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

  本发明提供了一种使用4,6-二取代或2,4,6-三取代喹唑啉衍生物的治疗病毒感染的方法，其结构式表示为[(I)]，其中：R2选自氢、NR′R″和C1-7烷基的组；—A选自键、O、S(O)n、C1-7烷基、C2-7烯基和C2-7炔基的组；R4选自C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代烷基和环烷基-烷基的组；—Y选自单键、C1-7烷基、C2-7烯基和C2-7炔基的组；n为0、1或2；R6选自卤素、杂芳基和芳基的组；以及其药学上可接受的加合物盐、立体异构体、单-或双-Λ/-氧化物、溶剂化合物或前药。
• WO2008/12326
  申请人：——

  公开号：——

  公开（公告）日：——
• Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk)
  作者：Andrew S. Rosenthal、Cordelle Tanega、Min Shen、Bryan T. Mott、James M. Bougie、Dac-Trung Nguyen、Tom Misteli、Douglas S. Auld、David J. Maloney、Craig J. Thomas

  DOI：10.1016/j.bmcl.2011.02.114

  日期：2011.5

  Continued examination of substituted 6-arylquinazolin-4-amines as Clk4 inhibitors resulted in selective inhibitors of Clk1, Clk4, Dyrk1A and Dyrk1B. Several of the most potent inhibitors were validated as being highly selective within a comprehensive kinome scan. Published by Elsevier Ltd.
• 2,4-SUBSTITUTED QUINAZOLINES AS LIPID KINASE INHIBITORS
  申请人：NOVARTIS AG

  公开号：EP2049502A1

  公开（公告）日：2009-04-22