6-(3,4-dimethoxyphenyl)-3H-quinazolin-4-one | 1003573-79-2

• 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-(3,4-dimethoxyphenyl)-3H-quinazolin-4-one
• CAS: 1003573-79-2
• 化学式: C₁₆H₁₄N₂O₃
• 分子量: 282.299
• InChiKey: BWZJDSXZHHEIOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(3,4-dimethoxyphenyl)-3H-quinazolin-4-one 在 氨 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 4-amino-6-(3,4-dimethoxyphenyl)-quinazoline
  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：

  2-氨基-5-溴苯甲酸乙酯 在 四(三苯基膦)钯 、 ammonium acetate 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 13.0h， 生成 6-(3,4-dimethoxyphenyl)-3H-quinazolin-4-one
  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

• 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。
• 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.
• Discovery of novel pyrrolidineoxy-substituted heteroaromatics as potent and selective PI3K delta inhibitors with improved physicochemical properties
  作者：Klemens Hoegenauer、Nicolas Soldermann、Christina Hebach、Gregory J. Hollingworth、Ian Lewis、Anette von Matt、Alexander B. Smith、Romain M. Wolf、Rainer Wilcken、Dorothea Haasen、Christoph Burkhart、Frédéric Zécri

  DOI：10.1016/j.bmcl.2016.10.069

  日期：2016.12

  In the recent years, PI3K delta has emerged as a promising target for the treatment of B-and T-cell mediated inflammatory diseases. We present a cellular assay activity analysis for our previously reported 4,6-diaryl quinazoline PI3K delta inhibitor series that suggests an optimal logP range between 2 and 3. We discovered novel analogues in this lipophilicity space that feature a chiral pyrrolidineoxy-group as a replacement for the position-4 aromatic ring of 4,6-diaryl quinazolines. These Fsp(3) enriched derivatives retain potency and selectivity towards PI3K delta. Compared to 4,6-diaryl quinazolines, their permeability profile is improved and molecular weight as well as PSA are reduced. These modifications offer additional possibilities for derivative generation in a favorable physicochemical property space and thus increase the chances to identify a clinical candidate. (C) 2016 Elsevier Ltd. All rights reserved.
• US8673929B2
  申请人：——

  公开号：US8673929B2

  公开（公告）日：2014-03-18
• [EN] 4,6-DL- AND 2,4,6-TRISUBSTITUTED QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING VIRAL INFECTIONS<br/>[FR] DÉRIVÉS QUINAZOLINE 4,6-DISUBSTITUÉS ET 2,4,6-TRISUBSTITUÉS ET COMPOSITIONS PHARMACEUTIQUES UTILES POUR TRAITER DES INFECTIONS VIRALES
  申请人：GILEAD SCIENCES INC

  公开号：WO2008009077A2

  公开（公告）日：2008-01-24

  [EN] 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: R₂ is selected from the group consisting of hydrogen, NR'R" and C_1-
  [FR] La présente invention concerne le traitement d'infections virales avec un dérivé quinazoline 4,6-disubstitué ou 2,4,6-trisubstitué représenté par la formule structurale [(I)] dans laquelle : R₂ est choisi dans le groupe constitué par un atome d'hydrogène, NR'R' et un groupe alkyle en C₁ à C₇ ; - A est choisi dans le groupe constitué par une liaison, O, S(O)_n, un groupe alkylène en C₁ à C₇, un groupe alcénylène en C₂ à C₇ et un groupe alcynylène en C₂ à C₇ ; R₄ est choisi dans le groupe constitué par un groupe alkyle en C₁ à C₇, un groupe alcényle en C₂ à C₇, un groupe cycloalkyle en C₃ à C₁₀, un groupe cycloalcényle en C₃ à C₁₀, un groupe aryle, un groupe hétérocyclique, un groupe arylalkyle, un groupe alkyle substitué par un groupe hétérocyclique et un groupe cycloalkyl-alkyle ; - Y est choisi dans le groupe constitué par une liaison simple, un groupe alkylène en C₁ à C₇, un groupe alcénylène en C₂ à C₇ et un groupe alcynylène en C₂ à C₇ ; n vaut 0, 1 ou 2 ; et R₆ est choisi dans le groupe constitué par un atome d'halogène, un groupe hétéroaryle et un groupe aryle ; un sel d'addition pharmaceutiquement acceptable, un stéréoisomère, un mono- ou di-?/-oxyde, un solvate ou un promédicament de celui-ci.