QSAR study on a novel series of 8-azaadenine analogues proposed as A1 adenosine receptor antagonists.
8-Azaadenines have been recently proposed as a novel promising class of adenosine A1 receptor antagonists. A QSAR study on 45 derivatives, synthesized in our laboratory as antagonists for A1 receptor, is described here. The use of the CODESSA program allowed obtaining a quite simple equation capable of correlating the structural features of these ligands to their activity toward A1 receptor. The model was investigated for reliability and stability by using statistical analysis criteria stricter than usual. Particular care was put in defining the chemical space where the model gave reliable predictions. The model allowed the identification of relevant structural features required for the interaction with the A1 receptor, enabling the prediction of activity of molecules belonging to focused virtual libraries.
Massarelli
Ilaria
I
Department of Chemistry and Industrial Chemistry, University of Pisa, via Risorgimento 35, 56126 Pisa, Italy.
Coi
Alessio
A
Pietra
Daniele
D
Nofal
Fatena Ahmad
FA
Biagi
Giuliana
G
Giorgi
Irene
I
Leonardi
Michele
M
Fiamingo
Francesca
F
Bianucci
Anna Maria
AM
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D021281:Quantitative Structure-Activity Relationship; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D015203:Reproducibility of Results; D012984:Software
D058916:Adenosine A1 Receptor Antagonists; D008024:Ligands; D043682:Receptor, Adenosine A1; D000225:Adenine; C006654:8-azaadenine