Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

  • Bioorg Med Chem Lett. 2009 Feb 1;19(3):1004-8. doi: 10.1016/j.bmcl.2008.11.058.
Kyle A Emmitte  1 ,  Brian J Wilson ,  Erich W Baum ,  Holly K Emerson ,  Kevin W Kuntz ,  Kristen E Nailor ,  James M Salovich ,  Stephon C Smith ,  Mui Cheung ,  Roseanne M Gerding ,  Kirk L Stevens ,  David E Uehling ,  Robert A Mook Jr ,  Ganesh S Moorthy ,  Scott H Dickerson ,  Anne M Hassell ,  M Anthony Leesnitzer ,  Lisa M Shewchuk ,  Arthur Groy ,  Jason L Rowand ,  Kelly Anderson ,  Charity L Atkins ,  Jingsong Yang ,  Peter Sabbatini ,  Rakesh Kumar
Affiliations
  • 1. GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. [email protected]
PMID: 19101143 DOI: 10.1016/j.bmcl.2008.11.058
Abstract

The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.