Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1374614 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
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.
Graphical abstractAnalogs utilizing proline isosteres in IGF-1R/IR inhibitors are disclosed. X-ray co-crystallography of selected analogs reveals information key to target potency.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
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Authors
Anthony J. Sampognaro, Mark D. Wittman, Joan M. Carboni, Chiehying Chang, Ann F. Greer, Warren W. Hurlburt, John S. Sack, Dolatrai M. Vyas,