title: 2-Aminoimidazoles inhibitors of TGF-beta receptor 1.
abstract: The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.
authors.affiliation: Abbot Laboratories, 381 Plantation Street, Worcester, MA 01605-2323, USA. dominique.bonafoux@abbott.com
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonafoux
authors.forename: Claudio
authors.initials: C
authors.lastname: Chuaqui
authors.forename: P Ann
authors.initials: PA
authors.lastname: Boriack-Sjodin
authors.forename: Chris
authors.initials: C
authors.lastname: Fitch
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hankins
authors.forename: Serene
authors.initials: S
authors.lastname: Josiah
authors.forename: Cheryl
authors.initials: C
authors.lastname: Black
authors.forename: Gregg
authors.initials: G
authors.lastname: Hetu
authors.forename: Leona
authors.initials: L
authors.lastname: Ling
authors.forename: Wen-Cherng
authors.initials: WC
authors.lastname: Lee
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D007093:Imidazoles; D018125:Receptors, Transforming Growth Factor beta; C014973:2-aminoimidazole; D008156:Luciferases