Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have be en synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethyla mine hydrobromide followed by the reaction of the product thus obtained wit h aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protec tion as compared to 77% protection offered by the standard Indomethacin. Qu antitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) pa rameter as independent and antithrombic activity as dependent parameter, wh ere antithrombotic activity correlated best (r > 0.8) with electronic param eters (F, sigma or mu) having high statistical significance > 99.9% (F-2,F- 22 > 15.0; F-2,F-22 alpha :0.001 = 11.0) suggesting that hydrophobic, steri c and resonance factors are insignificant in this set of molecules for the activity. (C) 2001 Elsevier Science Ltd. All rights reserved.