6,7-dimethoxy-N-(3-(methylthio)phenyl)quinazolin-4-amine hydrochloride | 1428015-46-6

• 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: 6,7-dimethoxy-N-(3-(methylthio)phenyl)quinazolin-4-amine hydrochloride
• 英文别名: 6,7-dimethoxy-N-(3-methylsulfanylphenyl)quinazolin-4-amine;hydrochloride
• CAS: 1428015-46-6
• 化学式: C₁₇H₁₇N₃O₂S*ClH
• 分子量: 363.868
• InChiKey: AQIHETRTMGYUSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  81.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-chloro-6,7-dimethoxylquinazoline hydrochloride 、 3-氨基茴香硫醚 以 异丙醇 为溶剂， 反应 4.0h， 以71%的产率得到6,7-dimethoxy-N-(3-(methylthio)phenyl)quinazolin-4-amine hydrochloride
  参考文献：
  名称：

  Synthesis, characterization, screening and docking analysis of 4-anilinoquinazoline derivatives as tyrosine kinase inhibitors

  摘要：

  We report here the design and synthesis of a series of 4-anilinoquinazoline derivatives, of which 7 compounds were crystallographically characterized, as epidermal growth factor receptor (EGFR) inhibitors by modifications on the aniline ring or at the 6-alkoxy site of the 6,7-dimethoxy-4-anilinoquinazoline pharmacophore. The relative inhibition efficiency on EGFR of all as-prepared compounds were measured and ordered, and the IC50 values of nine highly active compounds were determined by ELISA. Docking studies indicated that all 4-anilinoquinazoline derivatives could be inserted into the ATP-binding pocket of the EGFR via indirect docking, and that the modifications at the 3'-position of the anilino group and 6-alkoxy site of the quinazoline ring have little interference with the formation of the two essential H-bonds between the N3 of the quinazoline ring and Thr766 through a water molecule, and the N1 of the quinazoline ring and N-H of Met769. The displacing of the phenyl at 4-position with pyridinyl dramatically reduces the activity of the quinazoline pharmacophore, the resulting derivative (10) being the least active compound. The docking results also showed that the formation of new H-bonds between the N-H of the ethylenediamine group linked to the 6-alkoxy site and Asp776/Cys773 in the binding pocket of EGFR makes compounds 19 (IC50= 12.1 +/- 1.6 nM) and 20 (IC50 = 13.6 +/- 0.8 nM) the most potent EGFR inhibitors in this class and worthy of further modification to obtain more potent anticancer compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.036

文献信息

• SUBSTITUTED HETEROAROMATIC COMPOUNDS AND THEIR USE IN MEDICINE
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0782570A1

  公开（公告）日：1997-07-09
• [EN] SUBSTITUTED HETEROAROMATIC COMPOUNDS AND THEIR USE IN MEDICINE<br/>[FR] COMPOSES HETEROAROMATIQUES SUBSTITUES ET LEUR UTILISATION EN MEDECINE
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1996009294A1

  公开（公告）日：1996-03-28

  (EN) The invention is directed towards substituted heteroaromatic compounds which are protein tyrosine kinase inhibitors, in particular substituted quinolines and quinazolines. Methods of their preparation, pharmaceutical compositions including such compounds and their use in medicine, for example in the treatment of psoriasis, fibrosis, atherosclerosis, restenosis, auto-immune disease, allergy, asthma, transplantation rejection, inflammation, thrombosis, nervous system diseases, and cancer.(FR) On décrit des composés hétéroaromatiques substitués qui sont des inhibiteurs des tyrosines kinases, notamment des quinolines et quinazolines substituées. On décrit également des procédés de préparation de ces composés, des compositions pharmaceutiques comprenant de tels composés ainsi que l'utilisation de ceux-ci en médecine, par exemple dans le traitement du psoriasis, des fibroses, de l'athérosclérose, de la resténose, des maladies auto-immunes, des allergies, de l'asthme, du rejet de greffon, des inflammations, de la thrombose, des maladies du système nerveux et du cancer.