Comparison of inhibitory activity of isomeric triazolopyridine derivatives towards adenosine receptor subtypes or do similar structures reveal similar bioactivities?
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.
Guba
Wolfgang
W
F. Hoffmann-LaRoche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, Lead Generation, CH-4070 Basel, Switzerland.
Nettekoven
Matthias
M
Püllmann
Bernd
B
Riemer
Claus
C
Schmitt
Sébastien
S
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
D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines; D018047:Receptors, Purinergic P1; D014230:Triazoles