6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid | 1017969-37-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid
• 英文别名: 6-(6,7-dimethoxyquinazolin-4-yl)oxynaphthalene-1-carboxylic acid
• CAS: 1017969-37-7
• 化学式: C₂₁H₁₆N₂O₅
• 分子量: 376.368
• InChiKey: XWWMBEVYYTUBAX-UHFFFAOYSA-N

物化性质

• 沸点：
  614.4±50.0 °C(Predicted)
• 密度：
  1.367±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  90.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid 在 氯化亚砜 作用下， 生成
  参考文献：
  名称：

  Evaluation of a Series of Naphthamides as Potent, Orally Active Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitors

  摘要：

  We have previously shown N-arylnaphthamides can be potent inhibitors of vascular endothelial growth factor receptors (VEGFRs). N-Alkyl and N-unsubstituted naphthamides were prepared and found to yield nanomolar inhibitors of VEGFR-2 (KDR) with an improved selectivity profile against a panel of tyrosine and serine/threonine kinases. The inhibitory activity of this series was retained at the cellular level. Naphthamides 3, 20, and 22 exhibited good pharmacokinetics following oral dosing and showed potent inhibition of VEGF-induced angiogenesis in the rat corneal model. Once-daily oral administration of 22 for 14 days led to 85% inhibition of established HT29 colon cancer and Calu-6 lung cancer xenografts at doses of 10 and 20 mg/kg, respectively.

  DOI：

  10.1021/jm701098w
• 作为产物：
  描述：

  6-羟基-1-萘甲酸 、 4-氯-6,7-二甲氧基喹唑啉 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以59%的产率得到6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid
  参考文献：
  名称：

  Naphthamide Derivatives As Multi-Target Protein Kinase Inhibitors and Histone Deacetylase Inhibitors

  摘要：

  描述了具有化学式I的孤立化合物及其立体异构体、对映异构体、顺反异构体和药用可接受的盐，以及用于生产这些化合物和组合物的方法，以及用于治疗与异常蛋白激酶活性和/或异常组蛋白去乙酰化酶活性相关的疾病的方法和这些化合物和组合物的用途，包括炎症性疾病、自身免疫疾病、癌症、神经系统和神经退行性疾病、心血管疾病、代谢疾病、过敏和哮喘和/或与激素相关的疾病。

  公开号：

  US20100298358A1

文献信息

• Naphthamide Derivatives As Multi-Target Protein Kinase Inhibitors and Histone Deacetylase Inhibitors
  申请人：LU Xian-Ping

  公开号：US20100298358A1

  公开（公告）日：2010-11-25

  Isolated compounds of formula I: and stereoisomers, enantiomers, diastereomers, and pharmaceutically acceptable salts thereof are described, as well as processes for production, and methods of use of these compounds and compositions thereof for the treatment of diseases associated with abnormal protein kinase activities and/or abnormal histone deacetylase activities including, for example, inflammatory diseases, autoimmune diseases, cancer, neurological and neurodegenerative diseases, cardiovascular diseases, metabolic disease, allergies and asthma and/or hormone-related diseases.

  描述了具有化学式I的孤立化合物及其立体异构体、对映异构体、顺反异构体和药用可接受的盐，以及用于生产这些化合物和组合物的方法，以及用于治疗与异常蛋白激酶活性和/或异常组蛋白去乙酰化酶活性相关的疾病的方法和这些化合物和组合物的用途，包括炎症性疾病、自身免疫疾病、癌症、神经系统和神经退行性疾病、心血管疾病、代谢疾病、过敏和哮喘和/或与激素相关的疾病。
• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20060241115A1

  公开（公告）日：2006-10-26

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等具有有效性。本发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐，以及用于预防和治疗涉及癌症等疾病和其他疾病或状况的药物组合物和方法。该发明还涉及制备此类化合物的过程，以及在此类过程中有用的中间体。
• Naphthamide derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors
  申请人：Shenzhen Chipscreen Biosciences Ltd.

  公开号：US08211901B2

  公开（公告）日：2012-07-03

  Isolated compounds of formula I: and stereoisomers, enantiomers, diastereomers, and pharmaceutically acceptable salts thereof are described, as well as processes for production, and methods of use of these compounds and compositions thereof for the treatment of diseases associated with abnormal protein kinase activities and/or abnormal histone deacetylase activities including, for example, inflammatory diseases, autoimmune diseases, cancer, neurological and neurodegenerative diseases, cardiovascular diseases, metabolic disease, allergies and asthma and/or hormone-related diseases.

  本文描述了公式I的孤立化合物及其立体异构体、对映异构体、顺反异构体和药物可接受的盐，以及制备这些化合物和其组合物的方法，以及用于治疗与异常蛋白激酶活性和/或异常组蛋白去乙酰化酶活性相关的疾病的方法，包括但不限于炎症性疾病、自身免疫疾病、癌症、神经和神经退行性疾病、心血管疾病、代谢性疾病、过敏和哮喘和/或激素相关疾病。
• NAPHTHALENE CARBOXAMIDE DERIVATIVES AS INHIBITORS OF PROTEIN KINASE AND HISTONE DEACETYLASE, PREPARATION METHODS AND USES THEREOF
  申请人：Shenzhen Chipscreen Biosciences, Ltd.

  公开号：EP2439195B1

  公开（公告）日：2014-07-16
• COMPOUNDS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：EP1713484A2

  公开（公告）日：2006-10-25