Monocyclic thiophenes as protein tyrosine phosphatase 1B inhibitors: capturing interactions with Asp48

Zhao-Kui Wan; Jinbo Lee; Weixin Xu; David V Erbe; Diane Joseph-McCarthy; Bruce C Follows; Yan-Ling Zhang

doi:10.1016/j.bmcl.2006.06.051

Monocyclic thiophenes as protein tyrosine phosphatase 1B inhibitors: capturing interactions with Asp48

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4941-5. doi: 10.1016/j.bmcl.2006.06.051. Epub 2006 Jun 27.

Authors

Zhao-Kui Wan¹, Jinbo Lee, Weixin Xu, David V Erbe, Diane Joseph-McCarthy, Bruce C Follows, Yan-Ling Zhang

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.

PMID: 16806920
DOI: 10.1016/j.bmcl.2006.06.051

Abstract

A series of monocyclic thiophenes was designed and synthesized as PTP1B inhibitors. Guided by X-ray co-crystal structural information and computational modeling, rational design led to key interactions with Asp48 and improved inhibitory potency against PTP1B.

MeSH terms

Aspartic Acid / chemistry*
Aspartic Acid / metabolism
Crystallography, X-Ray
Cyclization
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Models, Molecular
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases / antagonists & inhibitors*
Protein Tyrosine Phosphatases / chemistry
Protein Tyrosine Phosphatases / metabolism*
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology*

Substances

Enzyme Inhibitors
Thiophenes
Aspartic Acid
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases