N¹-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine hydrochloride | 153437-70-8

• 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: N¹-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine hydrochloride
• 英文别名: 4-(4'-aminoanilino)-6,7-dimethoxyquinazoline hydrochloride；4-N-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine;hydrochloride
• CAS: 153437-70-8
• 化学式: C₁₆H₁₆N₄O₂*ClH
• 分子量: 332.79
• InChiKey: WIEWJZVAKXFUTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  23
• 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：
  82.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N¹-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine hydrochloride 、 5-叔丁基-3-异氰酰基异噁唑 在 N,N-二异丙基乙胺 作用下， 以 异丁酰胺 为溶剂， 生成 1-(5-Tert-butyl-1,2-oxazol-3-yl)-3-[4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]urea
  参考文献：
  名称：

  [EN] UREA DERIVATIVES AS KINASE MODULATORS
  [FR] DERIVES D'UREE EN TANT QUE MODULATEURS DE LA KINASE

  摘要：

  公开号：

  WO2005048948A3
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 在 palladium 10% on activated carbon 盐酸 、 氢气 作用下， 以 甲醇 、 正丁醇 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 3.0h， 生成 N¹-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine hydrochloride
  参考文献：
  名称：

  [EN] UREA DERIVATIVES AS KINASE MODULATORS
  [FR] DERIVES D'UREE EN TANT QUE MODULATEURS DE LA KINASE

  摘要：

  公开号：

  WO2005048948A3

文献信息

• Quinazoline derivatives as anti-proliferative agents
  申请人：Zeneca Limited

  公开号：US05616582A1

  公开（公告）日：1997-04-01

  The invention concerns quinazoline derivatives of the formula I ##STR1## wherein m is 1, 2 or 3 and each R.sup.1 includes hydroxy, amino, carboxy, carbamoyl, ureido, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbamoyl, N,N-di-[(1-4C)alkyl]carbamoyl, hydroxyamino, (1-4C)alkoxyamino, (2-4C)alkanoyloxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy and (1-3C)alkylenedioxy; n is 1 or 2 and each R.sup.2 includes hydrogen, hydroxy, halogeno, trifluoromethyl, amino, nitro, cyano and (1-4C)alkyl; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer.

  本发明涉及式I的喹唑啉衍生物：##STR1## 其中，m为1、2或3，每个R1包括羟基、氨基、羧基、氨基甲酰基、尿素基、（1-4C）烷氧基羰基、N-（1-4C）烷基氨甲酰基、N，N-二-[(1-4C)烷基]氨甲酰基、羟氨基、（1-4C）烷氧氨基、（2-4C）烷酰氧氨基、三氟甲氧基、（1-4C）烷基、（1-4C）烷氧基和（1-3C）烷二氧基；n为1或2，每个R2包括氢、羟基、卤素、三氟甲基、氨基、硝基、氰基和（1-4C）烷基；或其药学上可接受的盐；制备它们的方法；包含它们的制药组合物；以及利用化合物的受体酪氨酸激酶抑制性质治疗癌症。
• Quinazoline derivatives useful for treatment of neoplastic disease
  申请人：Zeneca Limited

  公开号：US05457105A1

  公开（公告）日：1995-10-10

  The invention concerns quinazoline derivatives of the formula I ##STR1## wherein m is 1, 2 or 3 and each R.sup.1 includes hydroxy, amino, carboxy, carbamoyl, ureido, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbamoyl, N,N-di-[(1-4C)alkyl]carbamoyl, hydroxyamino, (1-4C)alkoxyamino, (2-4C)alkanoyloxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy and (1-3C)alkylenedioxy; n is 1 or 2 and each R.sup.2 includes hydrogen, hydroxy, halogeno, trifluoromethyl, amino, nitro, cyano and (1-4C)alkyl; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer.

  本发明涉及公式I的喹唑啉衍生物：##STR1## 其中m为1、2或3，每个R1包括羟基、氨基、羧基、氨基甲酰基、尿素基、（1-4C）烷氧基羰基、N-(1-4C)烷基氨甲酰基、N，N-二[(1-4C)烷基]氨甲酰基、羟基氨基、(1-4C)烷氧基氨基、(2-4C)烷酰氧基氨基、三氟甲氧基、(1-4C)烷基、(1-4C)烷氧基和(1-3C)烷基二氧；n为1或2，每个R2包括氢、羟基、卤素、三氟甲基、氨基、硝基、氰基和(1-4C)烷基；或其药学上可接受的盐；制备它们的过程；包含它们的制药组合物；以及利用化合物的受体酪氨酸激酶抑制性质治疗癌症。
• Synthesis, characterization, screening and docking analysis of 4-anilinoquinazoline derivatives as tyrosine kinase inhibitors
  作者：Shuang Lü、Wei Zheng、Liyun Ji、Qun Luo、Xiang Hao、Xianchan Li、Fuyi Wang

  DOI：10.1016/j.ejmech.2012.07.036

  日期：2013.3

  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.
• Quinazoline derivatives
  申请人：ZENECA LIMITED

  公开号：EP0566226B1

  公开（公告）日：1995-11-08
• US5457105A
  申请人：——

  公开号：US5457105A

  公开（公告）日：1995-10-10