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

David R Adams; Achamma Abraham; Jun Asano; Catherine Breslin; Colin A J Dick; Ulrich Ixkes; Blair F Johnston; Derek Johnston; Justin Kewnay; Simon P Mackay; Simon J MacKenzie; Morag McFarlane; Lee Mitchell; Daniel Spinks; Yasuo Takano

doi:10.1016/j.bmcl.2007.09.069

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

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6579-83. doi: 10.1016/j.bmcl.2007.09.069. Epub 2007 Sep 25.

Authors

David R Adams¹, Achamma Abraham, Jun Asano, Catherine Breslin, Colin A J Dick, Ulrich Ixkes, Blair F Johnston, Derek Johnston, Justin Kewnay, Simon P Mackay, Simon J MacKenzie, Morag McFarlane, Lee Mitchell, Daniel Spinks, Yasuo Takano

Affiliation

¹ Department of Chemistry, School of Engineering & Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK. D.R.Adams@hw.ac.uk

PMID: 17931864
DOI: 10.1016/j.bmcl.2007.09.069

Abstract

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 degrees site exhibit 3-60microM IC(50)s for PTP1B inhibition in an Sf9 cell-based assay.

Publication types

Comparative Study

MeSH terms

Animals
Binding Sites
Cell Line
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / classification
Enzyme Inhibitors / metabolism
Ligands
Propionates / chemistry*
Propionates / classification*
Propionates / pharmacology
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Spodoptera / cytology

Substances

Enzyme Inhibitors
Ligands
Propionates
Protein Tyrosine Phosphatase, Non-Receptor Type 1