Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3810-5. doi: 10.1016/j.bmcl.2012.03.103. Epub 2012 Apr 11.

Abstract

We describe a new class of NO-donor hypoglycemic products obtained by joining tolbutamide, a typical hypoglycemic sulfonylurea, with a NO-donor moiety through a hard link. As NO-donors we chose either furoxan (1,2,5-oxadiazole 2-oxide) derivatives or the classical nitrooxy function. A preliminary biological characterization of these compounds, including stimulation of insulin release from cultured rat pancreatic β-cells and in vitro vasodilator and anti-aggregatory activities, is reported.

MeSH terms

  • Animals
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Nitric Oxide Donors / chemistry*
  • Rats
  • Sulfonylurea Compounds / chemistry
  • Tolbutamide / analogs & derivatives*
  • Tolbutamide / chemical synthesis
  • Tolbutamide / pharmacology
  • Vasodilator Agents / chemical synthesis*
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology

Substances

  • Hypoglycemic Agents
  • Insulin
  • Nitric Oxide Donors
  • Sulfonylurea Compounds
  • Vasodilator Agents
  • Tolbutamide