Synthesis and biological evaluation of (±)-3-(2-(2-fluorobenzyloxy) naphthalen-6-yl)-2-aminopropanoic acid derivatives as novel PTP1B inhibitors

Eur J Med Chem. 2011 Sep;46(9):3630-8. doi: 10.1016/j.ejmech.2011.05.027. Epub 2011 May 20.

Abstract

A series of novel nonphosphonate-based pTyr mimetics comprised (±)-3-(2-(2-fluorobenzyloxy)naphthalen-6-yl)-2-aminopropanoic acid derivatives were identified as reversible and competitive PTP1B inhibitors via a structure-based design approach. Among the compounds studied, 12h was found to have the best in vitro inhibition activity against PTP1B (IC(50) = 1.25 ± 0.24 μM) and the best selectivity (3-fold) between PTP1B and TCPTP. These results should provide suitable druglike lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Propionates / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*

Substances

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