Potent quinoxaline-Based inhibitors of PDGF receptor tyrosine kinase activity. Part 1: SAR Exploration and Effective Bioisosteric Replacement of a phenyl substituent

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 18; pp. 3091 - 3095
• Main Authors: Myers, Michael R., He, Wei, Hanney, Barbara, Setzer, Natalie, Maguire, Martin P., Zulli, Allison, Bilder, Glenda, Galzcinski, Helen, Amin, Dilip, Needle, Saul, Spada, Alfred P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.09.2003
• Subjects: Angioplasty, Balloon, Coronary - adverse effects; Aorta - cytology; Cell Division - drug effects; Coronary Restenosis - drug therapy; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Humans; Inhibitory Concentration 50; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Phosphorylation - drug effects; Protein-Tyrosine Kinases - antagonists & inhibitors; Quinoxalines - chemical synthesis; Quinoxalines - pharmacology; Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00654-1

Novel substituted 2-anilino- and 2-cycloalkylaminoquinoxalines have been found to be useful and selective inhibitors of PDGF-R autophosphorylation. Replacement of an anilino-substituent with substituted cyclohexylamino- or norbornylamino substituents led to significant improvements in the pharmacokinetic profile of these analogues. Novel substituted 2-anilino- and 2-cycloalkylaminoquinoxalines have been found to be useful and selective inhibitors of PDGF-R autophosphorylation. Replacement of an anilino-substituent with substituted cyclohexylamino- or norbornylamino-substituents led to significant improvements in the pharmacokinetic profile of these analogues.