Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B.

A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINC02765569 were synthesized and screened for PTP1B inhibitory activity. The most potent compounds 3-(1-(5-methoxy-1H-benzo[d]imidazol-2-ylthio)acetamido)-4-methyl benzoic acid (10c, IC₅₀ 8.2 μM) and 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC₅₀ 8.3 μM) showed maximum PTP1B inhibitory activity. Docking studies were also performed to understand the nature of interactions governing the binding mode of the designed molecules within the active site of the PTP1B enzyme.