Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.

SAR of benzoyl sulfathiazole derivatives as PTP1B inhibitors / 药学学报

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.