Inhibition of cyclic nucleotide phosphodiesterases from pig coronary artery by benzo-separated analogues of 3-isobutyl-1-methylxanthine.

The linear and proximal benzo-separated analogues of 7-benzyl-3-isobutyl-1-methylxanthine, 3-isobutyl-1,8-dimethylxanthine, 3-isobutyl-8-tert-butyl-1-methylxanthine, 3-isobutyl-8-(methoxymethyl)-1-methylxanthine , and 1-isoamyl-3-isobutylxanthine have been prepared and assayed as inhibitors of the peak I and peak II forms of cyclic nucleotide phosphodiesterase from pig coronary artery. Most of the benzo analogues were less effective inhibitors of these phosphodiesterases when compared to 3-isobutyl-1-methylxanthine (IBMX) even though the active sites of both enzyme forms tolerated the stretched-out xanthines. Indeed, the linear benzo-separated analogue of 7-benzyl-IBMX was a more potent inhibitor of peak I activity than was IBMX.