Discovery of novel and potent heterocyclic carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors.

Article Details

Citation

Copy to clipboard

Basu S, Prasad UV, Barawkar DA, De S, Palle VP, Menon S, Patel M, Thorat S, Singh UP, Das Sarma K, Waman Y, Niranjan S, Pathade V, Gaur A, Reddy S, Ansari S

Discovery of novel and potent heterocyclic carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors.

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2843-9. doi: 10.1016/j.bmcl.2012.02.070. Epub 2012 Mar 1.

PubMed ID

22424978 [ View in PubMed

]

Abstract

A series of novel heterocyclic carboxylic acid based protein tyrosine phosphatase 1B (PTP1B) inhibitors with hydrophobic tail have been synthesized and characterized. Structure-activity relationship (SAR) optimization resulted in identification of several potent, selective (over the highly homologous T-cell protein tyrosine phosphatase, TCPTP) and metabolically stable PTP1B inhibitors. Compounds 7a, 19a and 19c showed favorable cell permeability and pharmacokinetic properties in mouse with moderate to very good oral (% F=13-70) bio-availability.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
5-(2-Fluoro-5-{(1E)-3-[3-hydroxy-2-(methoxycarbonyl)phenoxy]-1-propen-1-yl}phenyl)-1,2-oxazole-3-carboxylic acid	Tyrosine-protein phosphatase non-receptor type 1	Ki (nM)	6900	N/A	N/A	Details