title: Synthesis of useful fragments in drug discovery: 2-Amino-5-tert-butylpyridine and its oxidised analogues.
abstract: 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.
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom. christopher.thomson@novartis.com
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Thomson
authors.forename: John
authors.initials: J
authors.lastname: Reilly
authors.forename: David A
authors.initials: DA
authors.lastname: Sandham
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D010084:Oxidation-Reduction; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000631:Aminopyridines; D011725:Pyridines; D012709:Serum Albumin; D003577:Cytochrome P-450 Enzyme System; C023666:pyridine