Structure-based optimization of benzoic acids as inhibitors of protein tyrosine phosphatase 1B and low molecular weight protein tyrosine phosphatase

ChemMedChem. 2009 Jun;4(6):957-62. doi: 10.1002/cmdc.200800427.

Abstract

We have optimized previously discovered benzoic acids 1, which are active as inhibitors of PTP1B and LMW-PTP, two protein tyrosine phosphatases that have emerged as attractive targets for the development of novel therapeutic agents for the treatment of diabetes, obesity, and cancer. Our efforts led to the identification of new and more potent analogues with appreciable selectivity toward human PTP1B and the IF1 isoform of human LMW-PTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / chemical synthesis
  • Benzoates / chemistry*
  • Benzoates / pharmacology
  • Catalytic Domain
  • Computer Simulation
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Benzoates
  • Enzyme Inhibitors
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • ACP1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases