Paper Citing NAMD - Abstract
Pittala, Valeria; Siracusa, Maria A.; Modica, Maria N.; Salerno, Loredana; Pedretti, Alessandro; Vistoli, Giulio; Cagnotto, Alfredo; Mennini, Tiziana; Romeo, Giuseppe
Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the alpha(1)-adrenoceptors
BIOORGANIC & MEDICINAL CHEMISTRY, 19:5260-5276, SEP 1 2011
Three different series of 1H-pyrrolopyrimidine-2,4-dione derivatives were designed and synthesized as ligands for the alpha(1)-adrenergic receptors (alpha(1)-ARs). A microwave-assisted protocol was developed in order to improve purity and yields of some final products. The majority of the synthesized compounds, tested in binding assays, displayed alpha(1)-AR affinities in the nanomolar range. Highest affinity values were found in derivatives 10b and 10c (K-i = 1.4 nM for both) whereas compound 10e was endowed with the best profile in term of alpha(1)-AR affinity (K-i = 2.71 nM) coupled with high selectivity towards 5-HT1A receptors (K-i > 10,000). Molecular docking studies were performed on human alpha(1)-ARs and human 5-HT1A receptors in order to rationalize the observed experimental affinity and selectivity; these computational studies helped to clarify molecular requirements for the design of high-selective alpha(1)-adrenergic ligands. (C) 2011 Elsevier Ltd. All rights reserved.
