Synthesis and cAMP-dependent phosphodiesterase inhibition of novel thiazoloquinazoline derivatives.

The series of 6,7,8,9-tetrahydro-5H-5-(2'-hydroxyphenyl)-2-(4'-substituted benzylidine)thiazolo(2,3-b)quinazolin-3(2H)-ones (4a-j) and 6,7,8,9-tetrahydro-5H-5-(2'-hydroxyphenyl)-2-(4'-substituted benzylidine)-3-(4-nitrophenyl amino)thiazoloquinazolines (5a-j) were synthesized by the reported method and evaluated for their phosphodiesterase inhibitory activity. All test compounds exhibited good activity. The structure-activity relationships were also studied. In both series of compounds, electron-withdrawing substitutions showed higher activity. Among the tested compounds, 6,7,8,9-tetrahydro-5H-5-(2'-hydroxyphenyl)-2-(4'-fluorobenzylidine)-3-(4-nitrophenylamino)thiazoloquinazoline (5e), 6,7,8,9-tetrahydro-5H-5-(2'-hydroxyphenyl)-2-(4'-nitrobenzylidine)-3-(4-nitrophenylamino)thiazoloquinazoline (5j) and 6,7,8,9-tetrahydro-5H-5-(2'-hydroxyphenyl)-2-(4'-chlorobenzylidine)-3-(4-nitrophenylamino)thiazoloquinazoline (5f) were found to be more potent than theophylline (IC50 in mmol L-1 of 1.34 ± 0.09 for 5f, 1.44 ± 0.02 for 5e, 1.52 ± 0.05 for 5jvs. 1.72 ± 0.09 for theophylline).