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

Abstract

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters ( F, σ or μ ) having high statistical significance > 99.9% (F_2,22 > 15.0; F_2,22α:0.001=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.