Synthesis, biological assays and QSAR studies of N-(9-benzyl-2-phenyl-8-azapurin-6-yl)-amides as ligands for A1 adenosine receptors

• Published in: Bioorganic & medicinal chemistry 2009-03, Vol.17 (5), p.1817-1830
• Main Authors: GIORGI, Irene, LEONARDI, Michele, PIETRA, Daniele, BIAGI, Giuliana, BORGHINI, Alice, MASSARELLI, Ilaria, CIAMPI, Osele, BIANUCCI, Anna Maria
• Format: Article
• Language: English
• Subjects: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Adenosine A3 Receptor Antagonists; Animals; Biological and medical sciences; Kinetics; Ligands; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Purines - chemical synthesis; Purines - chemistry; Purines - pharmacology; Quantitative Structure-Activity Relationship; Rats; Receptor, Adenosine A1 - chemistry; Receptor, Adenosine A2A - chemistry; Receptor, Adenosine A3 - chemistry
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.01.060

2-Phenyl-9-benzyl-8-azapurines, bearing at the 6 position an amido group interposed between the 8-azapurine moiety and an alkyl or a substituted phenyl group, have been synthesised and assayed as ligands for adenosine receptors. All the compounds show high affinity for the A(1) adenosine receptor, and many of them also show a good selectivity for A(1) with respect to A(2A) and A(3) adenosine receptors. Based on the quite rich library containing such compounds and relevant biological data, QSAR models, able to rationalise the results and to give a quantitative estimate of the observed trends were also developed. The obtained models can assist in the design of new compounds selectively active on A(1) adenosine receptor.