This paper reports the study of new 2-phenyl- and 2-methylpyrazolo[3,4-c] quinolin-4-ones (series A) and 4-amines (series B), designed as adenosine receptor (AR) antagonists. The synthesized compounds bear at the 6-position various groups, with different lipophilicity and steric hindrance, that were thought to increase human A1 and A2A AR affinities and selectivities, with respect to those of the parent 6-unsubstituted compounds. In series A, this modification was not tolerated since it reduced AR affinity, while in series B it shifted the binding towards the hA1 subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A2AAR-based homology models of the A1 and A3 ARs and at the A2AAR crystal structure were carried out.
Synthesis, structure-affinity relationships and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists
DAL BEN, DIEGO;LAMBERTUCCI, Catia;CRISTALLI, Gloria
2011-01-01
Abstract
This paper reports the study of new 2-phenyl- and 2-methylpyrazolo[3,4-c] quinolin-4-ones (series A) and 4-amines (series B), designed as adenosine receptor (AR) antagonists. The synthesized compounds bear at the 6-position various groups, with different lipophilicity and steric hindrance, that were thought to increase human A1 and A2A AR affinities and selectivities, with respect to those of the parent 6-unsubstituted compounds. In series A, this modification was not tolerated since it reduced AR affinity, while in series B it shifted the binding towards the hA1 subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A2AAR-based homology models of the A1 and A3 ARs and at the A2AAR crystal structure were carried out.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
