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

✍ Scribed by Anthony J. Sampognaro; Mark D. Wittman; Joan M. Carboni; Chiehying Chang; Ann F. Greer; Warren W. Hurlburt; John S. Sack; Dolatrai M. Vyas

• Book ID: 104004652
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 529 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.07.045

✦ Synopsis

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.