title: Synthesis, structure-affinity relationships, and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists.
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(2A)AR-based homology models of the A(1) and A(3) ARs and at the A(2A)AR crystal structure were carried out.
authors: Dipartimento di Scienze Farmaceutiche, Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi, Universita' di Firenze, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors: Ombretta
authors: O
authors: Lenzi
authors: Vittoria
authors: V
authors: Colotta
authors: Daniela
authors: D
authors: Catarzi
authors: Flavia
authors: F
authors: Varano
authors: Lucia
authors: L
authors: Squarcialupi
authors: Guido
authors: G
authors: Filacchioni
authors: Katia
authors: K
authors: Varani
authors: Fabrizio
authors: F
authors: Vincenzi
authors: Pier Andrea
authors: PA
authors: Borea
authors: Diego
authors: D
authors: Dal Ben
authors: Catia
authors: C
authors: Lambertucci
authors: Gloria
authors: G
authors: Cristalli