Design and structure–activity relationship of heterocyclic analogs of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones as inhibitors of receptor tyrosine kinases

• Published in: Bioorganic & medicinal chemistry letters 2006-04, Vol.16 (8), p.2247-2251
• Main Authors: Frazier, Kelly, Jazan, Elisa, McBride, Christopher M., Pecchi, Sabina, Renhowe, Paul A., Shafer, Cynthia M., Taylor, Clarke, Bussiere, Dirksen, He, Molly Min, Jansen, Johanna M., Lapointe, Gena, Ma, Sylvia, Vora, Jayesh, Wiesmann, Marion
• Format: Article
• Language: English
• Subjects: Basic fibroblast growth factor (bFGF); Benzimidazoles - chemical synthesis; Benzimidazoles - pharmacology; Biological and medical sciences; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - pharmacology; Hydroquinones - chemical synthesis; Hydroquinones - pharmacology; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; Platelet derived growth factor (PDGF); Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Structure-Activity Relationship; Vascular endothelial growth factor (VEGF)
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.01.020

The synthesis and SAR of a series of novel heterocyclic analogs of the 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one scaffold are reported. Herein are described a series of novel heterocyclic analogs of the 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one scaffold. These compounds are potent inhibitors of receptor tyrosine kinases and exhibit favorable pharmacokinetic profiles. The synthesis and SAR of these compounds are described.