Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Abstract

A series of some new 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines (1-6) have been evaluated in silico (docking studies) to recognize their hypothetical binding motif with the cyclooxygenase isoenzyme (COX-2) employing GLIDE software (Schrodinger Inc.) and in vivo (rat paw edema) for their antiinflammatory activities. The compound 6 with pyridyl substitution at the 6^th position of the thienopyrimidine moiety was found to form significant H-bonding interaction with crucial amino acid residue Arg 120 at a distance of 3 Å and exhibited good antiinflammatory activity [around 87 % of the standard: indomethacin]. The binding mode of the thienopyrimidines compounds have been proposed based on the docking studies. Further, the predicted ADME properties of all the tested compounds were found to be in the ranges as predicted by QikProp for 95 % of known oral drugs and also satisfy the Lipinski's rule of five.