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

作者：Rakse Monika; Karthikeyan Chandrabose; Deora Girdhar Singh; Moorthy N S H N; Rathore Vandana; Rawat Arun K; Srivastava A K; Trivedi Piyush^*

来源：European Journal of Medicinal Chemistry, 2013, 70: 469-476.

DOI：10.1016/j.ejmech.2013.10.030

• Diabetes
• PTP1B
• Acetamido benzoic acid derivatives
• Molecular modelling
• Lead optimization

A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINCO2765569 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 mu M) and 3-(2-(benzo[cljthiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC50 8.3 mu M) 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.

• 出版日期2013-12