title: 1,2,4-triazolo[3,4-a]pyridine as a novel, constrained template for fibrinogen receptor (GPIIb/IIIa) antagonists.
abstract: Conformationally constrained analogues of the GPIIb/IIIa antagonist elarofiban (RWJ-53308) have been synthesized and biologically evaluated. The 1,2,4-triazolo[3,4-a]pyridine scaffold provided potent antagonists with favorable pharmacodynamic and pharmacokinetic attributes in dogs. Compounds 12a and 13a exhibited enhancements in oral bioavailability, t(1/2), and ex vivo duration of action (inhibition of ADP-induced platelet aggregation) relative to elarofiban.
authors.affiliation: Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Lawson
authors.forename: W J
authors.initials: WJ
authors.lastname: Hoekstra
authors.forename: M F
authors.initials: MF
authors.lastname: Addo
authors.forename: P
authors.initials: P
authors.lastname: Andrade-Gordon
authors.forename: B P
authors.initials: BP
authors.lastname: Damiano
authors.forename: J A
authors.initials: JA
authors.lastname: Kauffman
authors.forename: J A
authors.initials: JA
authors.lastname: Mitchell
authors.forename: B E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D000818:Animals; D004285:Dogs; D009557:Nipecotic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
chemical_list: C439166:1,2,4-triazolo(3,4-a)pyridine; D009557:Nipecotic Acids; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011725:Pyridines; D014230:Triazoles; C402922:elarofiban