Synthesis and evaluation of some novel isochroman carboxylic acid derivatives as potential anti-diabetic agents

A series of novel isochroman 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. Analysis of structure–activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC50 value of 51.63 ± 0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.

Graphical abstractA series of novel isochroman-3(S)-carboxylic acids were synthesized, characterized and evaluated as potential anti-diabetic agents. Compound 4n inhibited PTP1B with IC50 of 51.63 ± 0.91 nM and showed significant reduction in fed-state and fasting WBG and fasting plasma glucose levels.Figure optionsDownload full-size imageDownload as PowerPoint slide