Bronchospasmolytic activity and adenosine receptor binding of some newer 1,3-dipropyl-8-phenyl substituted xanthine...

The aldehyde derivatives of 1,3-dipropyl xanthines as described in this paper, constitutes a new series of selective adenosine ligands displaying bronchospasmolytic activity. The effect of substitution at third- and fourth-position of 8-phenyl xanthine has also been taken into consideration. The synthesized compounds showed varying binding affinities at different adenosine receptor subtypes (A₁ , A_2A , A_2B , and A₃ ) and also good in vivo bronchospasmolytic activity against histamine aerosol-induced asthma in guinea pigs. Most of the compounds showed maximum affinity toward the A_2A receptor subtype. The monosubstituted 3-aminoalkoxyl 8-phenyl xanthine with a aminodiethyl moiety (compound 12e) was found to be most potent A_2A adenosine receptor ligand (K_i  = 0.036 µM) followed by disubstituted 4-aminoalkoxyl-3-methoxy-8-phenyl xanthine (K_i  = 0.050 µM) (compound 10a).