Downloaded By: [Anderson, Lee-Ann] At: 16:25 14 December 2007 Nucleosides, Nucleotides, and Nucleic Acids, 26:1443–1446, 2007 Copyright C  Taylor & Francis Group, LLC ISSN: 1525-7770 print / 1532-2335 online DOI: 10.1080/15257770701542264 SYNTHESIS AND BIOLOGICAL ACTIVITY OF TRISUBSTITUTED ADENINES AS A 2A ADENOSINE RECEPTOR ANTAGONISTS Catia Lambertucci, Sauro Vittori, Ram Chandra Mishra, and Diego Dal Ben ✷ Dipartimento di Scienze Chimiche, University of Camerino, Camerino (MC), Italy Karl-Norbert Klotz ✷ Institut f¨ ur Pharmakologie und Toxicologie, Universit¨ at of W¨ urzburg, W¨ urzburg, Germany Rosaria Volpini and Gloria Cristalli ✷ Dipartimento di Scienze Chimiche, University of Camerino, Camerino (MC), Italy ✷ The discovery of new drugs for the treatment of neurodegenerative disorders, such as Parkinson’s disease, has become an attractive field of research. Due to the regulation of D 2 receptor activity by A 2 A adenosine receptor, potent and selective ligands of A 2 A subtype could be useful tools to study neurodegenerative disorders. A series of 2,8-disubstituted-9-ethyladenine derivatives was synthesized and tested in binding affinity assay at human adenosine receptors. New compounds showed good affinity and selectivity at A 2 A receptor versus the other subtypes. The introduction of a bromine atom in 8-position increased the affinity of these compounds, leading to ligands with K i in the nanomolar range. Keywords Adenosine receptor ligands; adenosine receptor antagonits; A 2A antago- nists; 9-ethylpurine derivatives; substituted adenines INTRODUCTION Adenosine (Ado) is an endogenous modulator of a variety of physiolog- ical and pathophysiological processes that acts through the interaction with specific membrane receptors termed A 1 ,A 2A ,A 2B , and A 3 . [1] In particular, adenosine is deeply involved in the control of motor behaviour and substantial evidences indicate that adenosine A 2A receptor antagonists improve motor deficits in animal models of Parkinson’s disease. For this reason development of potent and selective A 2A adenosine receptor antagonists has become an attractive field for the discovery of new drugs This work was supported by Fondo di Ricerca di Ateneo (University of Camerino) and by grants from the Italian Ministry of Research: FIRB 2001, FIRB 2003, and PRIN 2005. Address correspondence to Catia Lambertucci, Dipartimento di Scienze Chimiche, Universit´ a di Camerino, I-62032 Camerino (MC), Italy. E-mail: catia.lambertucci@unicam.it 1443