Comparative molecular field analysis ( CoMFA) was performed to study the structure-activity relationship of novel benzofuranyl and benzothiophenyl biphenyls as protein tyrosine phophatase IB (PTP1B) inhibitors. In this analysis, three molecular fields were considered: electrostatic field, steric field and H-bond field. The value of cross- validated coefficient q~2 was found to be 0.58, showing that the model from CoMFA was good and the predictive biological activity of molecules in the test set indicated the predictive potential of the model for the untested compounds. It also indicated that the addition of H-bond field did improve the quality of the QSAR model. From analysis of the CoMFA coefficient contour plots, steric and electrostatic properties were identified, which were very helpful for designing new compounds. In addition, a newly developed approach, comparative molecular similarity indices analysis (CoMSIA), was tried. However, the results show that CoMSIA does not lead to any improvement compared with CoMFA for the system examined in this work.

Key words: BENZOFURAN;THIOPHENE P;DIPHENYL P;STRUCTURE ACTIVITY RELATIONSHIP, TYROSINE;PROTEIN;DIABETES MELLITUS