Synthesis of useful fragments in drug discovery: 2-Amino-5-tert-butylpyridine and its oxidised analogues

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4281-3. doi: 10.1016/j.bmcl.2011.05.066. Epub 2011 May 25.


A novel and robust synthesis of the fragment, 2-amino-5-tert-butylpyridine, has been described, which has been shown to have improved physicochemical properties over 4-tert-butylaniline, when considering drug-like properties. The synthesis also yields fragments containing more highly oxidised precursors to the tert-butyl group as intermediates. These fragments can be incorporated into final target molecules, yielding pharmaceutical compounds and their putative CYP-mediated oxidative metabolites, which can aid in elucidation of metabolic clearance processes.

MeSH terms

  • Aminopyridines / chemical synthesis
  • Aminopyridines / chemistry*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Evaluation, Preclinical
  • Humans
  • Oxidation-Reduction
  • Protein Binding
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Serum Albumin / chemistry


  • Aminopyridines
  • Pyridines
  • Serum Albumin
  • Cytochrome P-450 Enzyme System
  • pyridine