6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and antiangiogenic activity

Eur J Med Chem. 2014 May 6:78:126-39. doi: 10.1016/j.ejmech.2014.03.045. Epub 2014 Mar 17.

Abstract

A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a Buchwald-Hartwig amination reaction using palladium(0) transition metal, which certainly renders an expanded scope of amino substituents. Some analogs prepared using the methods described here showed high level of antiangiogenic and antitumor activities in chick chorioallantoic membrane (CAM) assay, demonstrating the potential of these new aminopyridinols as antiangiogenic agents.

Keywords: Aminopyridinol; Angiogenesis; Antiangiogenic; Antitumor; Chick chorioallantoic membrane assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Pyridones / chemical synthesis
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Pyridones
  • Vascular Endothelial Growth Factor A