title: 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.
abstract: 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.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA. anthony.sampognaro@bms.com
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Sampognaro
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wittman
authors.forename: Joan M
authors.initials: JM
authors.lastname: Carboni
authors.forename: Chiehying
authors.initials: C
authors.lastname: Chang
authors.forename: Ann F
authors.initials: AF
authors.lastname: Greer
authors.forename: Warren W
authors.initials: WW
authors.lastname: Hurlburt
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
mesh_terms: D008958:Models, Molecular; D011392:Proline / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors*; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D014227:Triazines; D011392:Proline; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin