7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-chloro-5-isopropoxyquinazoline | 692060-25-6

• 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: 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-chloro-5-isopropoxyquinazoline
• 英文别名: 7-[2-(4-Acetylpiperazin-1-yl)ethoxy]-4-chloro-5-isopropoxyquinazoline；1-[4-[2-(4-chloro-5-propan-2-yloxyquinazolin-7-yl)oxyethyl]piperazin-1-yl]ethanone
• CAS: 692060-25-6
• 化学式: C₁₉H₂₅ClN₄O₃
• 分子量: 392.885
• InChiKey: KNPXKYYKTNLBPI-UHFFFAOYSA-N

物化性质

• 沸点：
  585.7±50.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-chloro-5-isopropoxyquinazoline 、 3-氯-6-甲氧基-2-吡嗪胺 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-(2-chloro-5-methoxypyrazin-3-ylamino)-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
• 作为产物：
  描述：

  5,7-二氟-3,4-二氢喹唑啉-4-酮 在 四氯化碳 、 potassium tert-butylate 、 sodium hydride 、 三苯基膦 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 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-chloro-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] QUINAZOLINE DERIVATIVES AS SRC TYROSINE KINASE INHIBITORS<br/>[FR] DERIVES DE QUINAZOLINE UTILISES COMME INHIBITEURS DE SRC TYROSINE KINASE
  申请人：ASTRAZENECA AB

  公开号：WO2004041829A1

  公开（公告）日：2004-05-21

  The invention concerns quinazoline derivatives of Formula (I): (A chemical formula should be inserted here - please see paper copy enclosed herewith) wherein Z is an O, S, SO, SO2, N(R2) or C(R2)2 group wherein each R2 group is hydrogen or (1-8C) alkyl, m is 0, 1, 2 or 3, each R1 group is selected from halogeno, (1-8C) alkyl, (1-6C) alkoxy and any of the other meanings defined in the description, n is 0, 1, 2 or 3, and each R3 group is selected from halogeno, (1-8C) alkyl, (1-6C) alkoxy and any of the other meanings defined in the description, 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）的喹唑啉衍生物：其中Z是O、S、SO、SO2、N（R2）或C（R2）2基团，其中每个R2基团是氢或（1-8C）烷基，m为0、1、2或3，每个R1基团选自卤代烷基、（1-8C）烷基、（1-6C）烷氧基和描述中定义的其他含义，n为0、1、2或3，每个R3基团选自卤代烷基、（1-8C）烷基、（1-6C）烷氧基和描述中定义的其他含义，或其药用盐，其制备方法，含有它们的药物组合物以及它们在制备用作抗侵袭剂的药物中的使用，用于抑制和/或治疗实体肿瘤疾病。
• [EN] PYRAZINIL QUINAZOLINE DERIVATIVES FOR USE IN THE TREATMENT OF TUMOURS<br/>[FR] DERIVES PYRAZINILE QUINAZOLINE DESTINES AU TRAITEMENT DE TUMEURS
  申请人：ASTRAZENECA AB

  公开号：WO2004108711A1

  公开（公告）日：2004-12-16

  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 (1-8C)alkyl, m is 1, 2 or 3, each R1 group has any of the meanings defined in the description, Ra is hydrogen or halogeno, Rc is (1-6C)alkoxy and Rd is hydrogen, halogeno, (1-8C)alkyl or (1-6C)alkoxy, or a pharmaceutically-acceptable salt 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)的喹唑啉衍生物，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(1-8C)烷基，m为1、2或3，每个R1基团具有描述中定义的任何含义，Ra是氢或卤素，Rc是(1-6C)烷氧基，Rd是氢、卤素、(1-8C)烷基或(1-6C)烷氧基，或其药学上可接受的盐；它们的制备方法；含有它们的制药组合物及其在制造用作抗侵袭剂的药物中的使用，用于控制和/或治疗实体肿瘤疾病。
• [EN] QUINAZOLINE DERIVATIVES<br/>[FR] DERIVES QUINAZOLINIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2004056801A1

  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)的喹唑啉衍生物，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基团从卤代、(1-6C)烷基、(1-6C)烷氧基和描述中定义的其他含义中选择，Ra为氢或卤代，Rb为氢、卤代、(1-6C)烷基或(1-6C)烷氧基，Rc为(1-6C)烷氧基，Rd为氢、卤代、(1-6C)烷基或(1-6C)烷氧基，或其药学上可接受的盐；它们的制备方法，含有它们的药物组合物以及它们在制造用作抗侵袭剂的药物中的用途，用于抑制和/或治疗实体肿瘤疾病。
• [EN] 4-PYRIMIDINYL QUINAZOLINE DERIVATIVES FOR USE IN THE TREATMENT OF TUMOURS<br/>[FR] DERIVES 4-PYRIMIDINYLQUINAZOLINE A UTILISER DANS LE TRAITEMENT DE TUMEURS
  申请人：ASTRAZENECA AB

  公开号：WO2004108710A1

  公开（公告）日：2004-12-16

  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 (1-8C) alkyl, m is 1, 2 or 3, each R1 group has any of the meanings defined in the description, Ra is hydrogen or halogeno, Rb is hydrogen, halogeno, (1-8C) alkyl or (1-6C) alkoxy, and Rd is (1-6C) alkoxy, or a pharmaceutically-acceptable salt 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.

  该发明涉及公式（I）的喹唑啉衍生物，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（1-8C）烷基，m为1、2或3，每个R1基团具有在说明书中定义的任何含义，Ra是氢或卤素，Rb是氢、卤素、（1-8C）烷基或（1-6C）烷氧基，Rd为（1-6C）烷氧基，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它们在制造用于抗侵袭剂治疗和/或治疗实体肿瘤疾病的药物中的使用。
• Combination product of inhibitor of the src family of non-recetpor tyrosine kinases and gemcitabine
  申请人：Barge Alan

  公开号：US20060142297A1

  公开（公告）日：2006-06-29

  The invention concerns a combination comprising an inhibitor of Src kinase and the cytotoxic agent gemcitabine, a pharmaceutical composition comprising such a combination and its use in the treatment or prophylaxis of cancer, particularly of pancreatic cancer.

  本发明涉及一种组合物，包括Src激酶抑制剂和细胞毒素吉西他滨，一种含有该组合物的药物组合物以及其在治疗或预防癌症，特别是胰腺癌方面的用途。