4-(6,7-dimethoxyquinazolin-4-yloxy)-phenol | 347157-31-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(6,7-dimethoxyquinazolin-4-yloxy)-phenol
• 英文别名: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenol；4-(6,7-dimethoxyquinazolin-4-yl)oxyphenol
• CAS: 347157-31-7
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: UPMFOGCXEOLUAL-UHFFFAOYSA-N

物化性质

• 沸点：
  483.2±45.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 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：
  73.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(6,7-dimethoxyquinazolin-4-yloxy)-phenol 在 硝酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 18.0h， 以59%的产率得到4-(6,7-dimethoxyquinazolin-4-yloxy)-2-nitrophenol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i
• 作为产物：
  描述：

  4-苄氧基苯酚 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~85.0 ℃ 、101.33 kPa 条件下， 反应 104.17h， 生成 4-(6,7-dimethoxyquinazolin-4-yloxy)-phenol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i

文献信息

• [EN] FUSED AZOLES SUCH AS 2,5-DISUBSTITUTED BENZIMIDAZOLES, BENZOXAZOLES AND BENZOTHIAZOLES AS KINASE INHIBITORS<br/>[FR] AZOLES FUSIONNES TELS QUE BENZIMIDAZOLES, BENZOXAZOLES ET BENZOTHIAZLES 2,5-DISUBSTITUES COMME INHIBITEURS DE KINASE
  申请人：AMGEN INC

  公开号：WO2004085425A1

  公开（公告）日：2004-10-07

  The invention relates to compounds of the formulae (I) to (III) wherein the substituents are as defined in the specification. These compounds have kinase inhibitory activity, such as VEGFR/KDR inhibitory activity. Accordingly, the compounds of the formulae (I) to (III) would be useful in the prevention and treatment of angiogenesis related disorders, ophthalmological conditions, proliferative diseases, inflammatory diseases, and other pathological conditions as described in the specification.

  这项发明涉及式(I)至(III)的化合物，其中取代基如规范中所定义。这些化合物具有激酶抑制活性，如VEGFR/KDR抑制活性。因此，式(I)至(III)的化合物在预防和治疗与血管生成相关的疾病、眼科疾病、增生性疾病、炎症性疾病以及规范中描述的其他病理状况中将会有用。
• Heterocyclic compounds and methods of use
  申请人：——

  公开号：US20040209892A1

  公开（公告）日：2004-10-21

  Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis 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.

  选定的化合物对于预防和治疗血管生成介导的疾病等疾病有效。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、药物组合物以及预防和治疗癌症等疾病和其他疾病或病况的方法。本发明还涉及制备这些化合物的过程以及在这些过程中有用的中间体。
• Quinoline and quinazoline derivatives and drugs containing the same
  申请人：——

  公开号：US20040132727A1

  公开（公告）日：2004-07-08

  There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: 1 wherein R 1 and R 2 represent hydrogen, alkyl or the like; R 3 , R 4 , R 5 and R 6 represent hydrogen, halogen, alkyl, alkoxy or the like; R 11 and R 12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R 3 , R 4 , R 5 and R 6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R 19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

  提供了一些化合物，可用于治疗由PDGF受体自磷酸化介导的疾病，特别是可抑制新内膜形成肥大的化合物。这些化合物由式（I）或其药理学上可接受的盐或溶剂表示：1其中R1和R2表示氢，烷基或类似物；R3、R4、R5和R6表示氢，卤素，烷基，烷氧基或类似物；R11和R12表示氢，烷基，烷基羰基或类似物；而A表示公式（i）到（x）中的任意一个，但其中R3、R4、R5和R6表示氢，A表示组（v）其中u为0（零）且R19表示苯基，可选地被卤素，烷基或烷氧基取代的化合物被排除。
• QUINOLINE AND QUINAZOLINE DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1243582A1

  公开（公告）日：2002-09-25

  There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: wherein R1 and R2 represent hydrogen, alkyl or the like; R3, R4, R5, and R6 represent hydrogen, halogen, alkyl, alkoxy or the like; R11 and R12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R3, R4, R5 and R6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

  提供了可用于治疗由 PDGF 受体自身磷酸化介导的疾病的化合物，特别是可抑制新内膜形成肥厚的化合物。这些化合物是式 (I) 所代表的化合物或其药理学上可接受的盐或溶液： 其中 R1 和 R2 代表氢、烷基或类似物；R3、R4、R5 和 R6 代表氢、卤素、烷基、烷氧基或类似物；R11 和 R12 代表氢、烷基、烷基羰基或类似物；A 代表式(i)至(x)中的任意一种，但不包括 R3、R4、R5 和 R6 代表氢且 A 代表基团(v)（其中 u 为 0（零）且 R19 代表任选被卤素、烷基或烷氧基取代的苯基）的化合物。
• US7135466B2
  申请人：——

  公开号：US7135466B2

  公开（公告）日：2006-11-14