4-(3-amino-5-chloro-4-hydroxyphenoxy)-pyridine-2-carboxylic acid methylamide | 952490-52-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-amino-5-chloro-4-hydroxyphenoxy)-pyridine-2-carboxylic acid methylamide
• 英文别名: 4-(3-amino-5-chloro-4-hydroxyphenoxy)-N-methylpyridine-2-carboxamide
• CAS: 952490-52-7
• 化学式: C₁₃H₁₂ClN₃O₃
• 分子量: 293.71
• InChiKey: QAVDPIAJQMSDGR-UHFFFAOYSA-N

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：
  0.08
• 拓扑面积：
  97.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-5-isothiocyanatobenzyl)-4-methyl-piperazine 、 4-(3-amino-5-chloro-4-hydroxyphenoxy)-pyridine-2-carboxylic acid methylamide 在 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide 作用下， 以 乙腈 为溶剂， 反应 21.0h， 以24 mg的产率得到4-{7-chloro-2-[4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenylamino]-benzoxazol-5-yloxy}-pyridine-2-carboxylic acid methylamide
  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：

  N-甲基-4-氯-2-吡啶甲酰胺 在 乙醇 、 硝酸 、 sodium hydride 、 溶剂黄146 、 三氟乙酸 、 tin(ll) chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.67h， 生成 4-(3-amino-5-chloro-4-hydroxyphenoxy)-pyridine-2-carboxylic acid methylamide
  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

• 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).