New pyrazolo[3,4-b]pyridones as selective A1 adenosine receptor antagonists: synthesis, biological evaluation and molecular modelling studies

Paola Fossa; Marco Pestarino; Giulia Menozzi; Luisa Mosti; Silvia Schenone; Angelo Ranise; Francesco Bondavalli; M. Letizia Trincavelli; Antonio Lucacchini; Claudia Martini

doi:10.1039/B502831K

New pyrazolo[3,4-b]pyridones as selective A₁ adenosine receptor antagonists: synthesis, biological evaluation and molecular modelling studies

Paola Fossa,^a Marco Pestarino,^a Giulia Menozzi,*^a Luisa Mosti,^a Silvia Schenone,^a Angelo Ranise,^a Francesco Bondavalli,^a M. Letizia Trincavelli,^b Antonio Lucacchini^b and Claudia Martini^b

Author affiliations

* Corresponding authors

^a Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV 3, Genova, Italy
E-mail: menozzi@unige.it
Fax: +39 010 3538358
Tel: +39 010 3538351

^b Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Via Bonanno Pisano 6, Pisa, Italy
Fax: +39 050 2219609
Tel: +39 050 2219526

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 (5a–j) has been synthesized as potential A₁ adenosine receptor (A₁ AR) ligands. Binding affinities of the new compounds were determined for adenosine A₁, A_2A and A₃ receptors. Compounds 5b and 5g showed good affinity (K_i = 299 nM and 517 nM, respectively) and selectivity towards A₁ AR, whereas 5f showed good affinity for A_2A AR (K_i = 290 nM), higher than towards A₁ AR (K_i = 1000 nM). The only arylamino derivative of the series 5j displayed high affinity (K_i = 4.6 nM) and selectivity for A₃ AR. Molecular modelling and 3D-QSAR (CoMFA) studies carried out on the most active compounds gave further support to the pharmacological results.

Organic & Biomolecular Chemistry

New pyrazolo[3,4-b]pyridones as selective A₁ adenosine receptor antagonists: synthesis, biological evaluation and molecular modelling studies

Abstract

Additions and corrections

Article information

Download Citation

Permissions

New pyrazolo[3,4-b]pyridones as selective A₁ adenosine receptor antagonists: synthesis, biological evaluation and molecular modelling studies

Social activity

Search articles by author

Spotlight

Advertisements