Identification of a novel class of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents with protein tyrosine phosphatase inhibitory activity

Bioorg Med Chem Lett. 2003 Sep 1;13(17):2895-8. doi: 10.1016/s0960-894x(03)00623-1.

Abstract

A novel series of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents have been identified. These compounds show non-selective inhibitory properties against a panel of protein tyrosine phosphatases including PTP1B. Compounds 12 and 13 display oral glucose lowering effects in ob/ob mice.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Blood Glucose / drug effects
  • Diamines / chemical synthesis
  • Diamines / pharmacokinetics
  • Diamines / pharmacology*
  • Disease Models, Animal
  • Dithiothreitol / chemistry
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Triazines / chemistry
  • Triazines / pharmacokinetics
  • Triazines / pharmacology*

Substances

  • Blood Glucose
  • Diamines
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Triazines
  • Protein Tyrosine Phosphatases
  • Dithiothreitol