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 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, sigma or mu) having high statistical significance > 99.9% (F(2,22)>15.0; F(2,22alpha:0.001)=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.
Saxena
A K
AK
Division of Medicinal Chemistry, Central Drug Research Institute, -226 001, Lucknow, India. anilsak@hotmail.com
Pandey
S K
SK
Seth
P
P
Singh
M P
MP
Dikshit
M
M
Carpy
A
A
D000818:Animals; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy
D005343:Fibrinolytic Agents; D013844:Thiazoles