title: Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 1: SAR exploration and effective bioisosteric replacement of a phenyl substituent.
abstract: 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.
authors.affiliation: Aventis Pharmaceuticals, Route 202/206, Bridgewater, NJ 08807, USA. myers_michael_r@lilly.com
authors.forename: Michael R
authors.initials: MR
authors.lastname: Myers
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Barbara
authors.initials: B
authors.lastname: Hanney
authors.forename: Natalie
authors.initials: N
authors.lastname: Setzer
authors.forename: Martin P
authors.initials: MP
authors.lastname: Maguire
authors.forename: Allison
authors.initials: A
authors.lastname: Zulli
authors.forename: Glenda
authors.initials: G
authors.lastname: Bilder
authors.forename: Helen
authors.initials: H
authors.lastname: Galzcinski
authors.forename: Dilip
authors.initials: D
authors.lastname: Amin
authors.forename: Saul
authors.initials: S
authors.lastname: Needle
authors.forename: Alfred P
authors.initials: AP
authors.lastname: Spada
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D023903:Coronary Restenosis / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011810:Quinoxalines; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor