title: New pyrazolo[3,4-b]pyridones as selective A(1) adenosine receptor antagonists: synthesis, biological evaluation and molecular modelling studies.
abstract: A series of ethyl 4-amino-1-(2-chloro-2-phenylethyl)-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylates () has been synthesized as potential A(1) adenosine receptor (A(1) AR) ligands. Binding affinities of the new compounds were determined for adenosine A(1), A(2A) and A(3) receptors. Compounds and showed good affinity (K(i)= 299 nM and 517 nM, respectively) and selectivity towards A(1) AR, whereas showed good affinity for A(2A) AR (K(i)= 290 nM), higher than towards A(1) AR (K(i)= 1000 nM). The only arylamino derivative of the series displayed high affinity (K(i)= 4.6 nM) and selectivity for A(3) AR. Molecular modelling and 3D-QSAR (CoMFA) studies carried out on the most active compounds gave further support to the pharmacological results.
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
authors: Paola
authors: P
authors: Fossa
authors: Marco
authors: M
authors: Pestarino
authors: Giulia
authors: G
authors: Menozzi
authors: Luisa
authors: L
authors: Mosti
authors: Silvia
authors: S
authors: Schenone
authors: Angelo
authors: A
authors: Ranise
authors: Francesco
authors: F
authors: Bondavalli
authors: M Letizia
authors: ML
authors: Trincavelli
authors: Antonio
authors: A
authors: Lucacchini
authors: Claudia
authors: C
authors: Martini
mesh_terms: D008958:Models, Molecular; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; C447480:pyrazolo(3,4-b)pyridine