title: Synthesis and cAMP-dependent phosphodiesterase inhibition of novel thiazoloquinazoline derivatives.
abstract: 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).
authors.affiliation: Department of Biotechnology, Acharya Nagarjuna University, Guntur-522510, India. tpsphc@gmail.com
authors.forename: Theivendren Panneer
authors.initials: TP
authors.lastname: Selvam
authors.forename: Palanirajan Vijayaraj
authors.initials: PV
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; D013806:Theophylline; D000242:Cyclic AMP