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 A 1 and A 2A 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 hA 1 subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A 2AAR-based homology models of the A 1 and A 3 ARs and at the A 2AAR crystal structure were carried out. © 2011 Elsevier Ltd. All rights reserved.

Synthesis, structure-affinity relationships, and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists

VARANI, Katia;VINCENZI, Fabrizio;BOREA, Pier Andrea;
2011

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 A 1 and A 2A 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 hA 1 subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A 2AAR-based homology models of the A 1 and A 3 ARs and at the A 2AAR crystal structure were carried out. © 2011 Elsevier Ltd. All rights reserved.
2011
Lenzi, O; Colotta, V; Catarzi, D; Varano, F; Squarcialupi, L; Filacchioni, G; Varani, Katia; Vincenzi, Fabrizio; Borea, Pier Andrea; Ben, Dd; Lambertu...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1453114
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