4-(5-chloro-2-methoxypyridin-4-ylamino)-7-(2, 4-dimethoxybenzyloxy) - 5-isopropoxyquinazoline | 719304-92-4

• 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: 4-(5-chloro-2-methoxypyridin-4-ylamino)-7-(2, 4-dimethoxybenzyloxy) - 5-isopropoxyquinazoline
• 英文别名: 4-(5-Chloro-2-methoxypyridin-4-ylamino)-7-(2,4-dimethoxybenzyloxy)-5-isopropoxyquinazoline；N-(5-chloro-2-methoxypyridin-4-yl)-7-[(2,4-dimethoxyphenyl)methoxy]-5-propan-2-yloxyquinazolin-4-amine
• CAS: 719304-92-4
• 化学式: C₂₆H₂₇ClN₄O₅
• 分子量: 510.977
• InChiKey: RCRDTMFOYSWDDK-UHFFFAOYSA-N

物化性质

• 沸点：
  631.6±55.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(5-chloro-2-methoxypyridin-4-ylamino)-7-(2, 4-dimethoxybenzyloxy) - 5-isopropoxyquinazoline 在 caesium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5-chloro-2-methoxy-pyridin-4-yl)-[7-(3-chloro-propoxy)-5-isopropoxy-quinazolin-4-yl]-amine
  参考文献：
  名称：

  New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors

  摘要：

  A series of 5,7-disubstituted quinazolines, bearing 4-heteroaryl substituents such as 2-pyridinylamine or 2-pyrazinylamine, has been synthetised and evaluated as c-Src kinase inhibitors. Highly potent inhibition, high selectivity and physical properties suitable for oral dosing were achieved within this series: 23d and 42 were identified as sub-0.1 mu M inhibitors in a c-Src-driven cell proliferation assay and displayed adequate rat pharmacokinetics after oral administration. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.106
• 作为产物：
  描述：

  5,7-二氟-3,4-二氢喹唑啉-4-酮 在 potassium tert-butylate 、 sodium hexamethyldisilazane 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(5-chloro-2-methoxypyridin-4-ylamino)-7-(2, 4-dimethoxybenzyloxy) - 5-isopropoxyquinazoline
  参考文献：
  名称：

  New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors

  摘要：

  A series of 5,7-disubstituted quinazolines, bearing 4-heteroaryl substituents such as 2-pyridinylamine or 2-pyrazinylamine, has been synthetised and evaluated as c-Src kinase inhibitors. Highly potent inhibition, high selectivity and physical properties suitable for oral dosing were achieved within this series: 23d and 42 were identified as sub-0.1 mu M inhibitors in a c-Src-driven cell proliferation assay and displayed adequate rat pharmacokinetics after oral administration. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.106

文献信息

• [EN] 4- (PYRIDIN-4-YLAMINO) -QUINAZOLINE DERIVATIVES AS ANTI-TUMOR AGENTS<br/>[FR] DERIVES DE 4-(PYRIDIN-4-YLAMINO)-QUINAZOLINE UTILISES COMME AGENTS ANTICANCEREUX
  申请人：ASTRAZENECA AB

  公开号：WO2004056812A1

  公开（公告）日：2004-07-08

  The invention concerns quinazoline derivatives of Formula (I): wherein Z is an O, S, SO, SO2, N(R2) or C(R2)(R3) group wherein each R2 or R3 group is hydrogen or (1-6C)alkyl, m is 1, 2 or 3, each R1 group is selected from halogeno, (1-6C)alkyl, (1-6C)alkoxy and any of the other meanings defined in the description, Ra is hydrogen or halogeno, Rb is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy, Rc is (1-6C)alkoxy, and Rd is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy, or pharmaceutically-acceptable salts thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  该发明涉及式（I）的喹嗪啉衍生物：其中Z是O，S，SO，SO2，N（R2）或C（R2）（R3）基团，其中每个R2或R3基团是氢或（1-6C）烷基，m为1、2或3，每个R1基团选自卤代，（1-6C）烷基，（1-6C）烷氧基和描述中定义的任何其他含义，Ra是氢或卤代，Rb是氢，卤代，（1-6C）烷基或（1-6C）烷氧基，Rc是（1-6C）烷氧基，Rd是氢，卤代，（1-6C）烷基或（1-6C）烷氧基，或其药学上可接受的盐；制备它们的过程，含有它们的制药组合物以及它们在制造用于抗侵袭剂在固体肿瘤病的控制和/或治疗中使用的药物的制备中的用途。
• New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors
  作者：Bernard Barlaam、Mike Fennell、Hervé Germain、Tim Green、Laurent Hennequin、Rémy Morgentin、Annie Olivier、Patrick Plé、Michel Vautier、Gerard Costello

  DOI：10.1016/j.bmcl.2005.08.106

  日期：2005.12

  A series of 5,7-disubstituted quinazolines, bearing 4-heteroaryl substituents such as 2-pyridinylamine or 2-pyrazinylamine, has been synthetised and evaluated as c-Src kinase inhibitors. Highly potent inhibition, high selectivity and physical properties suitable for oral dosing were achieved within this series: 23d and 42 were identified as sub-0.1 mu M inhibitors in a c-Src-driven cell proliferation assay and displayed adequate rat pharmacokinetics after oral administration. (c) 2005 Elsevier Ltd. All rights reserved.