Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents

A series of novel dibenzo[b,d]furan mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Structure–activity relationship study led to the identification of potent compound 5E which inhibited PTP1B with IC50 value of 82 ± 0.43 nM. Compound 5E was screened in vivo as drug candidate for anti-diabetic activity using rosiglitazone maleate as the standard. Compound 5E showed significant reduction in body weight, fed-state whole blood glucose (WBG), fasting WBG, plasma glucose and plasma cholesterol levels and non-significant reduction in fasting plasma triglyceride levels in ob/ob mice.

Graphical abstractA series of dibenzo[b,d]furan carboxylic acids were synthesized and evaluated for anti-diabetic activity. Compound 5E inhibited PTP1B with IC50 of 82 nM and reduced WBG and plasma glucose in ob/ob mice.Figure optionsDownload full-size imageDownload as PowerPoint slide