Protein tyrosine phosphatase 1B (PTP-1B) has recently received much attention as a potential drug target in type 2 diabetes. T-cell protein tyrosine phosphatase (TCPTP) has an 80% homology to PTP-1B in the catalytic domains, and non-selective inhibition gives rise to severe side effects. Benzotriazole derivatives were found to be potent PTP-1B inhibitors, which provide a moderate degree of selectivity to PTP-1B over TCPTP. The 3D-QSAR and 3D-QSSR studies were conducted by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), to obtain the best CoMFA and CoMSIA models. The result indicates that the hydrogen bond formed by Arg24 in PTP-1B and benzotriazole molecules is of great importance for the selectivity of the compounds. An enormous, negatively charged and hydrogen-bond donor group at R2 of benzotriazole skeleton would be beneficial for increasing the activity of the compounds, and an enormous, positively charged and hydrogen-bond acceptor group at the end of the R2 position would increase the selectivity of benzotriazole derivatives.

Key words: benzotriazole, protein tyrosine phosphatase 1B, T-cell protein tyrosine phosphatase, 3D- QSAR/QSSR