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

Lenzi, O; Colotta, V; Catarzi, D; Varano, F; Squarcialupi, L; Filacchioni, G; Varani, K; Vincenzi, F; Borea, Pa; Dal Ben, D; Lambertucci, C; Cristalli, G

doi:10.1016/j.bmc.2011.05.001

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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.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11581/217680

Titolo:	Synthesis, structure-affinity relationships and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists
Autori interni:	DAL BEN, DIEGO LAMBERTUCCI, Catia CRISTALLI, Gloria
Data di pubblicazione:	2011
Rivista:	BIOORGANIC & MEDICINAL CHEMISTRY
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.
Handle:	http://hdl.handle.net/11581/217680
Appare nelle tipologie:	Articolo

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