2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: A new class of protein tyrosine phosphatase 1B inhibitors

A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme’s primary site and a hydrophobic chlorophenylthiazole extension in its 2° site exhibit 3–60 μM IC50s for PTP1B inhibition in an Sf9 cell-based assay.

Graphical abstractA new series of protein tyrosine phosphatase 1B inhibitors with a 2-aryl-3,3,3-trifluoro-2-hydroxypropionic acid core unit targeted at the enzyme’s primary site and a hydrophobic chlorophenylthiazole extension in the 2° site exhibit low-μM inhibitory activity in cell-based assays.Figure optionsDownload full-size imageDownload as PowerPoint slide