title: Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 2: the synthesis and biological activities of RPR127963 an orally bioavailable inhibitor.
abstract: RPR127963 demonstrates an excellent pharmacokinetic profile in several species and was found to be efficacious in the prevention of restenosis in a Yucatan mini-pig model upon oral administration of 1-5 mg/kg. The in vitro selectivity profile and SAR of the highly optimized PDGF-R tyrosine kinase inhibitor are highlighted.
authors.affiliation: Aventis Pharmaceuticals, Route 202/206, Brigdewater, NJ 08807, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Michael R
authors.initials: MR
authors.lastname: Myers
authors.forename: Barbara
authors.initials: B
authors.lastname: Hanney
authors.forename: Alfred P
authors.initials: AP
authors.lastname: Spada
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: Ken
authors.initials: K
authors.lastname: Page
authors.forename: Zaid
authors.initials: Z
authors.lastname: Jayyosi
authors.forename: Mark H
authors.initials: MH
authors.lastname: Perrone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D011810:Quinoxalines; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor