title: Comparison of inhibitory activity of isomeric triazolopyridine derivatives towards adenosine receptor subtypes or do similar structures reveal similar bioactivities?
abstract: The synthesis of an array of 8-amino-2-aryl-[1,2,4]triazolo[1,5-a]pyridine-6-carboxyl amide derivatives is described for the first time. A subset of 20 derivatives were compared to their isomeric 5-amino-2-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxyl amide counterparts with regard to their potential to inhibit the human adenosine 2a (hA2a) receptor and their selectivity against the human adenosine 1 (hA1) receptor. Based on the analysis of H-bond donor/acceptor capabilities of the isomeric triazolopyridine pairs it can be concluded that the H-bond donor strength of the free amino functionality is the main determinant for hA2a inhibitory activity and hA1 selectivity.
authors.affiliation: F. Hoffmann-LaRoche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, Lead Generation, CH-4070 Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guba
authors.forename: Matthias
authors.initials: M
authors.lastname: Nettekoven
authors.forename: Bernd
authors.initials: B
authors.lastname: Püllmann
authors.forename: Claus
authors.initials: C
authors.lastname: Riemer
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schmitt
mesh_terms: D001665:Binding Sites; D006801:Humans; D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines; D018047:Receptors, Purinergic P1; D014230:Triazoles