Synthesis and biological activity of trisubstituted adenines as A 2A adenosine receptor antagonists.
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(2A) adenosine receptor, potent and selective ligands of A(2A) 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(2A) 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.
Lambertucci
Catia
C
Dipartimento di Scienze Chimiche, Università di Camerino, I-62032 Camerino, MC, Italy. catia.lambertucci@unicam.it
Vittori
Sauro
S
Mishra
Ram Chandra
RC
Dal Ben
Diego
D
Klotz
Karl-Norbert
KN
Volpini
Rosaria
R
Cristalli
Gloria
G
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans
D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; C001172:9-ethyladenine; D000225:Adenine