Synthesis and PTP1B inhibition of 1,2-naphthoquinone derivatives as potent anti-diabetic agents

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1941-6. doi: 10.1016/s0960-894x(02)00331-1.

Abstract

A new series of 1,2-naphthoquinone derivatives was synthesized by various synthetic methods and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B). 1,2-Naphthoquinone derivatives with substituent at R(4) position showed submicromolar inhibitory activity, and compound 24 demonstrated 10- to 60-fold selectivity against the tested phosphatases. Also, several 4-aryl-1,2-naphthoquinone derivatives with substituents at R(3), R(6), R(7), or/and R(8) showed submicromolar inhibitory activity and good plasma stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacology*
  • Inhibitory Concentration 50
  • Naphthoquinones / chemistry*
  • Naphthoquinones / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Naphthoquinones
  • 1,2-naphthoquinone
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases