1,2,4-Triazolo[3,4-a]pyridine as a novel, constrained template for fibrinogen receptor (GP11b/111a) antagonists

Authors
Lawson, EC Hoekstra, WJ Addo, MF Andrade-Gordon, P Damiano, BP Kauffman, JA Mitchell, JA Maryanoff, BE
Citation
Ec. Lawson et al., 1,2,4-Triazolo[3,4-a]pyridine as a novel, constrained template for fibrinogen receptor (GP11b/111a) antagonists, BIOORG MED, 11(19), 2001, pp. 2619-2622
Citations number
13
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
19
Year of publication
2001
Pages
2619 - 2622
Database
ISI
SICI code
0960-894X(20011008)11:19<2619:1AANCT>2.0.ZU;2-R
Abstract
Conformationally constrained analogues of the GPIIb/IIIa antagonist elarofi ban (RWJ-53308) have been synthesized and biologically evaluated. The 1,2,4 -triazolo[3,4-a]pyridine scaffold provided potent antagonists with favorabl e pharmacodynamic and pharmacokinetic attributes in dogs. Compounds 12a and 13a exhibited enhancements in oral bioavailability, t(1/2), and ex vivo du ration of action (inhibition of ADP-induced platelet aggregation) relative to elarofiban. (C) 2001 Elsevier Science Ltd. All rights reserved.