4-(4-hydroxy-3-nitro-phenoxy)-pyridine-2-carboxylic acid amide | 952490-72-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-hydroxy-3-nitro-phenoxy)-pyridine-2-carboxylic acid amide
• 英文别名: 4-(4-Hydroxy-3-nitrophenoxy)picolinamide；4-(4-hydroxy-3-nitrophenoxy)pyridine-2-carboxamide
• CAS: 952490-72-1
• 化学式: C₁₂H₉N₃O₅
• 分子量: 275.221
• InChiKey: CMMQQPVYEKLKFS-UHFFFAOYSA-N

物化性质

• 沸点：
  474.3±45.0 °C(Predicted)
• 密度：
  1.510±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxy-3-nitro-phenoxy)-pyridine-2-carboxylic acid amide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 以90%的产率得到4-(3-amino-4-hydroxy-phenoxy)-pyridine-2-carboxylic acid amide
  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 、 硝酸 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~85.0 ℃ 、101.33 kPa 条件下， 反应 122.17h， 生成 4-(4-hydroxy-3-nitro-phenoxy)-pyridine-2-carboxylic acid amide
  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。
• FUSED AZOLES SUCH AS 2,5-DISUBSTITUTED BENZIMIDAZOLES, BENZOXAZOLES AND BENZOTHIAZOLES AS KINASE INHIBITORS
  申请人：AMGEN INC.

  公开号：EP1638954A1

  公开（公告）日：2006-03-29
• US7531553B2
  申请人：——

  公开号：US7531553B2

  公开（公告）日：2009-05-12
• Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors
  作者：Michele H. Potashman、James Bready、Angela Coxon、Thomas M. DeMelfi,、Lucian DiPietro、Nicholas Doerr、Daniel Elbaum、Juan Estrada、Paul Gallant、Julie Germain、Yan Gu、Jean-Christophe Harmange、Stephen A. Kaufman、Rick Kendall、Joseph L. Kim、Gondi N. Kumar、Alexander M. Long、Seshadri Neervannan、Vinod F. Patel、Anthony Polverino、Paul Rose、Simon van der Plas、Douglas Whittington、Roger Zanon、Huilin Zhao

  DOI：10.1021/jm070034i

  日期：2007.9.1

  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).