Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase.
Bioorganic & medicinal chemistry letters 2010 Jul 15; In press
Sampognaro A AJ, Wittman M MD, Carboni J JM, Chang C, Greer A AF, Hurlburt W WW, Sack J JS, Vyas D DM
Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, P.O. Box 5400, Princeton, NJ 08543-5400, USA.
Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as isosteric proline replacements in a series of insulin-like growth factor I receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in potency to proline-containing reference compounds were shown to project a key fluoropyridine amide into a common space, while less potent compounds were not able to do so for reasons of stereochemistry or structural rigidity.
Keywords: IGF-1R kinase
