Design and synthesis of furoxan-based nitric oxide-releasing glucocorticoid derivatives with potent anti-inflammatory activity and improved safety

Bioorg Med Chem Lett. 2007 Feb 15;17(4):1062-6. doi: 10.1016/j.bmcl.2006.11.018. Epub 2006 Nov 10.

Abstract

A series of furoxan-based nitric oxide-releasing glucocorticoid derivatives was synthesized. The pharmacological assays indicated that three compounds, including I(4), I(5), and I(6), had anti-inflammatory activity. Furthermore compared with the leading compound hydrocortisone the safety of I(6) was greatly improved. Due to releasing NO in vivo the side effects of glucocorticoids, including hypertension and osteoporosis, were effectively avoided.

MeSH terms

  • Alkaline Phosphatase / antagonists & inhibitors
  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology*
  • Blood Pressure / drug effects
  • Carrageenan
  • Cell Proliferation / drug effects
  • Cotton Fiber
  • Dose-Response Relationship, Drug
  • Drug Design
  • Edema / chemically induced
  • Edema / pathology
  • Edema / prevention & control
  • Glucocorticoids / adverse effects
  • Glucocorticoids / chemical synthesis*
  • Glucocorticoids / pharmacology*
  • Heart Rate / drug effects
  • Mice
  • Nitric Oxide / metabolism*
  • Osteoblasts / drug effects
  • Osteoclasts / drug effects
  • Oxadiazoles / adverse effects
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship
  • Xylenes

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Oxadiazoles
  • Xylenes
  • furoxans
  • Nitric Oxide
  • Carrageenan
  • Alkaline Phosphatase