Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5732-4. doi: 10.1016/j.bmcl.2010.08.008. Epub 2010 Aug 7.

Abstract

A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B inhibition of 31.58% and 35.90% at 100 μM concentration. The compound 4a also showed 40.3% normalization of plasma glucose levels at 100mg/kg in Sugar-loaded model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies of these molecules revealed that hydrogen bond formation with Arg221 is important for activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Computer Simulation
  • Diabetes Mellitus, Experimental / drug therapy
  • Disease Models, Animal
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use
  • Piperazine
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / therapeutic use
  • Propanols / chemical synthesis
  • Propanols / chemistry*
  • Propanols / therapeutic use
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Rats

Substances

  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Piperazines
  • Propanols
  • Piperazine
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1