INSIGHT INTO AMINOMETHYL-PIPERIDONES BASED DPP-IV INHIBITORS FOR TREATMENT OF DIABETES: AN APPLICATION OF RATIONAL DRUG DESIGN

DPP IV is an important biological target for treatment of diabetes. The CoMFA, CoMSIA and HQSAR models have been developed on thirty two aminomethyl piperidones derivatives. The data set consisting of twenty one training set compounds and eleven test set compounds that showed good statistical significance with internal cross validation (q2) 0.849, 0.790 and 0.901, non-cross validation (r2) 0.863, 0.793 and 0.903 and predicted (pred. r2) 0.845, 0.822 and 0.901 for CoMFA, CoMSIA and HQSAR, respectively for anti-diabetic activity. The docking study explored with active site of DPP IV, in particular, the contribution of the –NH, 2,5 di-F (Ar) with Asn 151, Asn 169 and Asn 170 of the compound 22, respectively, which is important for the bioactive conformation for DPP IV inhibition. The QSAR models, contour maps, and docking binding affinity obtained could be successfully utilized as a guiding tool for design and discovery of novel derivatives.