Abstract
Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.
MeSH terms
-
Animals
-
COS Cells
-
Carboxylic Acids / chemical synthesis
-
Carboxylic Acids / chemistry
-
Carboxylic Acids / pharmacology*
-
Chlorocebus aethiops
-
Crystallography, X-Ray
-
Isoxazoles / chemical synthesis
-
Isoxazoles / chemistry
-
Isoxazoles / pharmacology*
-
Models, Molecular
-
Molecular Structure
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatases / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Carboxylic Acids
-
Isoxazoles
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatases