Please use this identifier to cite or link to this item: https://doi.org/10.1021/jm300899q
Title: Exploring the directionality of 5-substitutions in a new series of 5-alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine as a strategy to design novel human A3 adenosine receptor antagonists
Authors: Federico, S.
Ciancetta, A.
Sabbadin, D.
Paoletta, S.
Pastorin, G. 
Cacciari, B.
Klotz, K.N.
Moro, S.
Spalluto, G.
Issue Date: 26-Nov-2012
Citation: Federico, S., Ciancetta, A., Sabbadin, D., Paoletta, S., Pastorin, G., Cacciari, B., Klotz, K.N., Moro, S., Spalluto, G. (2012-11-26). Exploring the directionality of 5-substitutions in a new series of 5-alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine as a strategy to design novel human A3 adenosine receptor antagonists. Journal of Medicinal Chemistry 55 (22) : 9654-9668. ScholarBank@NUS Repository. https://doi.org/10.1021/jm300899q
Abstract: The structure-activity relationship (SAR) of new 5-alkylaminopyrazolo[4,3- e]1,2,4-triazolo[1,5-c]pyrimidines as antagonists of the A3 adenosine receptor (AR) was explored with the principal aim to establish the directionality of 5-substitutions inside the orthosteric binding site of the A3 AR. All the synthesized compounds showed affinity for the hA 3 AR from nanomolar to subnanomolar range. In particular, the most potent and selective antagonist presents an (S) α-phenylethylamino moiety at the 5 position (26, Ki hA3 = 0.3 nM). Using an in silico receptor-driven approach, we have determined the most favorable orientation of the substitutions at the 5 position of the pyrazolo[4,3-e]1,2,4- triazolo[1,5-c]pyrimidine (PTP) scaffold, opening the possibility for further derivatizations aimed at directing the N5 position toward the extracellular environment. © 2012 American Chemical Society.
Source Title: Journal of Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/105949
ISSN: 00222623
DOI: 10.1021/jm300899q
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