1,2,4-triazolo[3,4-a]pyridine as a novel, constrained template for fibrinogen receptor (GPIIb/IIIa) antagonists

E C Lawson; W J Hoekstra; M F Addo; P Andrade-Gordon; B P Damiano; J A Kauffman; J A Mitchell; B E Maryanoff

doi:10.1016/s0960-894x(01)00529-7

1,2,4-triazolo[3,4-a]pyridine as a novel, constrained template for fibrinogen receptor (GPIIb/IIIa) antagonists

Bioorg Med Chem Lett. 2001 Oct 8;11(19):2619-22. doi: 10.1016/s0960-894x(01)00529-7.

Authors

E C Lawson¹, W J Hoekstra, M F Addo, P Andrade-Gordon, B P Damiano, J A Kauffman, J A Mitchell, B E Maryanoff

Affiliation

¹ Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA.

PMID: 11551763
DOI: 10.1016/s0960-894x(01)00529-7

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.

MeSH terms

Animals
Dogs
Nipecotic Acids / chemical synthesis
Nipecotic Acids / chemistry
Nipecotic Acids / pharmacokinetics
Nipecotic Acids / pharmacology*
Platelet Aggregation Inhibitors / chemical synthesis
Platelet Aggregation Inhibitors / chemistry
Platelet Aggregation Inhibitors / pharmacokinetics
Platelet Aggregation Inhibitors / pharmacology*
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacokinetics
Pyridines / pharmacology*
Triazoles / chemistry*

Substances

1,2,4-triazolo(3,4-a)pyridine
Nipecotic Acids
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Pyridines
Triazoles
elarofiban