Acta Pharm. 61 (2011) 103-113

 

full paper

Short communication

 

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

THEIVENDREN PANNEER SELVAM and PALANIRAJAN VIJAYARAJ KUMAR

tpsphc@gmail.com

1 Department of Biotechnology, Acharya Nagarjuna University, Guntur-522510, India

2 Department of Pharmacy, College Sadaya, International University, Jalan Menara Gading 56000 Cheras, Kuala Lumpur, Malaysia

Accepted February 16, 2011

 

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-nitrophenylamino)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 L1 of 1.34 0.09 for 5f, 1.44 0.02 for 5e, 1.52 0.05 for 5j vs. 1.72 0.09 for theophylline).

 

Keywords: thiazoloquinazoline, benzylidinethiazoloquinazoline, nitrophenylaminothiazolo quinazoline, phosphodiesterase inhibition, SAR