3-D-QSAR analysis of 2-(oxalylamino) benzoic acid class of protein tyrosine phosphatase 1B inhibitors by CoMFA and Cerius2.GA

Three-Dimensional Quantitative Structure -Activity Relationship (3-D-QSAR) studies for 2-(oxalylamino) benzoic acids as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors were performed using the genetic function approximation algorithm (Cerius2.GA) and Comparative Molecular Field Analysis (CoMFA). A five-term equation was developed with crossvalidated r(2) (r(CV)(2)) and conventional correlation coefficient (r(2)) of 0.642 and 0.748, respectively, using Cerius2.GA. The CoMFA model from multifit alignment produced good statistical significance with r(CV)(2) and r(2) of 0.671 and 0.900, respectively. The predictive abilities of Cerius2.GA and CoMFA were determined using a test set of ten molecules giving predictive correlation coefficients of 0.666 and 0.643, respectively, indicating good predictive power. Furthermore, the robustness of the models was verified by bootstrapping analysis. Based on the information derived from Cerius2.GA and CoMFA, we have identified some key features that may be used to design new derivatives and predict their PTP affinities prior to synthesis.