The manuscript titled Adenine based acyclic-nucleotides as novel P2X3 receptor ligands has been accepted for publication in Journal of Medicinal Chemistry published by American Chemical Society.
Authors: Volpini Rosaria; Mishra, RC; Kachare DD; Dalben Diego; Catia Lambertucci; Ippolito Antonini; Vittori sauro; Marucci Gabriella and Nistri Andrea
![Reblog this post [with Zemanta]](http://img.zemanta.com/reblog_e.png?x-id=3cdce9b6-c73b-44f4-8a85-8717c7b7fe71)
The article titled above has been published in the Journal CHEMMEDCHEM.
Special Issue: XIX NMMC Verona 2008
Published Online: 2 Apr 2009
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA
Full Paper
|
Adenosine A2A Receptor Antagonists: New 8-Substituted 9-Ethyladenines as Tools for in vivo Rat Models of Parkinson’s Disease
|
| Rosaria Volpini, Prof. 1 *, Diego Dal Ben, Dr. 1, Catia Lambertucci, Dr. 1, Gabriella Marucci, Prof. Dr. 1, Ram Chandra Mishra, Dr. 1, Anna Teresa Ramadori, Dr. 1, Karl-Norbert Klotz, Prof. 2, Maria Letizia Trincavelli, Dr. 3, Claudia Martini, Prof. 3, Gloria Cristalli, Prof. 1 |
| 1Dipartimento di Scienze Chimiche, Università di Camerino via S. Agostino 1, 62032 Camerino (MC) (Italy), Fax: (+39) 0737-402295 2Institut für Pharmakologie und Toxikologie, Versbacher Str. 9, 97078 Würzburg (Germany) 3Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno Pisano 6, 56010 Pisa (Italy) |
| email: Rosaria Volpini (rosaria.volpini@unicam.it) |
*Correspondence to Rosaria Volpini, 1Dipartimento di Scienze Chimiche, Università di Camerino via S. Agostino 1, 62032 Camerino (MC) (Italy), Fax: (+39) 0737-402295
Funded by:
Italian Ministry for University and Research; Grant Number: PRIN2006, FIRB RBN503YA3L project
| Keywords |
| adenosine • antagonists • molecular modeling • purine derivatives • receptors |
| Abstract |
| A new series of 8-substituted 9-ethyladenine derivatives has been synthesized and tested at rat and human adenosine receptors. Binding data demonstrates that some compounds could represent new tools suitable for in vivo studies in rat models of Parkinson’s disease and for the design of new molecules with improved affinity and selectivity at human AA2AR. |
| Clinical evidence has demonstrated that AA2AR antagonists could be an alternative approach to the treatment of Parkinson’s disease. Recently, three 9-ethyladenine derivatives bearing a bromine atom, an ethoxy group, and a furyl ring, respectively, in the 8-position have been reported to ameliorate motor deficits in rat Parkinson’s disease models, suggesting a potential therapeutic role for these compounds. Starting from these observations, a new series of 9-ethyladenine derivatives, bearing different substituents such as halogens, alkoxy groups, aromatic and heteroaromatic rings in the 8-position, were synthesized. Radioligand binding assays demonstrated that some of the new compounds bind rat AA2AR with higher affinity than the previously reported congeners and that there is a good correlation between binding to rat and human receptors. Hence, the new molecules could represent new tools suitable for the in vivo studies in rat models of Parkinson’s disease. Finally, a molecular docking analysis of the compounds was performed using a homology model of rat AA2AR, built using the human crystal structure as the template, and results are in agreement with the binding data. |
| Digital Object Identifier (DOI) |
10.1002/cmdc.200800434 About DOI
![Reblog this post [with Zemanta]](http://img.zemanta.com/reblog_e.png?x-id=79ed6c1a-ee32-4942-8e9f-2b722668b11a)