Computational drug design in the search of protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents

Computational approaches, including both indirect and direct designs have been used in the search of novel small molecules as potential biologically active agents. The protein tyrosine phosphatase 1B (PTP1B) is been considered is potential targets for designing for antidiabetic agents as PTP1B inhibition results both in increased insulin sensitivity and resistance to obesity, with no abnormalities in growth or fertility or other pathogenetic effects. Thus in search of small molecule as potential PTP1B inhibitors, the indirect drug design approaches like CoMFA, CoMSIA and pharmacophore modeling resulted in the design and synthesis of a series of 2-[(4-methoxyphenyl) ethyl] acetamide derivatives including a promising PTP1B inhibitor (IC50 = 69μM) and another series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols where one compound showed 40.3% normalization of plasma glucose levels at 100mg/kg in sugar-loaded model (SLM) and 32% activity in streptozocin model (STZ).