The receptor binding affinity data to adenosine A(1) and A(2a) receptors of a wide series of 8-ethenyl-xanthine derivatives has been analyzed by means of the Free-Wilson model. The analysis of the individual group contributions (alpha ij) Shows the importance of the presence of an ethenyl moiety at position 8 on the xanthine ring for obtaining selective A(2a) antagonists. The different aii values of the substituents for the adenosine A(1) receptor do not correlate with the corresponding ones fbr the A?a receptor, indicating the possibility to obtain A(1) and A(2a) Selective compounds. The presence of aromatic substituents at the 8-ethenyl group, such as 3,5-(OCH3)(2)-phenyl, permits to obtain strongly A(2a) Selective compounds (affinity ratio of up to 100); moreover, it appears that 8-ethenyl-xanthinic derivatives cannot have high selectivity for the adenosine A(1) receptor (affinity ratio less than or equal to 10).
De novo analysis of receptor binding affinity data of 8-ethenyl-xanthine antagonists to adenosine A1 and A2A receptors
DALPIAZ, Alessandro;GESSI, Stefania;VARANI, Katia;BOREA, Pier Andrea
1997
Abstract
The receptor binding affinity data to adenosine A(1) and A(2a) receptors of a wide series of 8-ethenyl-xanthine derivatives has been analyzed by means of the Free-Wilson model. The analysis of the individual group contributions (alpha ij) Shows the importance of the presence of an ethenyl moiety at position 8 on the xanthine ring for obtaining selective A(2a) antagonists. The different aii values of the substituents for the adenosine A(1) receptor do not correlate with the corresponding ones fbr the A?a receptor, indicating the possibility to obtain A(1) and A(2a) Selective compounds. The presence of aromatic substituents at the 8-ethenyl group, such as 3,5-(OCH3)(2)-phenyl, permits to obtain strongly A(2a) Selective compounds (affinity ratio of up to 100); moreover, it appears that 8-ethenyl-xanthinic derivatives cannot have high selectivity for the adenosine A(1) receptor (affinity ratio less than or equal to 10).I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.