Chemical modification of ovatodiolide revealed a promising amino-prodrug with improved pharmacokinetic profile

Chem Commun (Camb). 2020 Sep 25;56(75):11018-11021. doi: 10.1039/c9cc07573a. Epub 2020 Aug 28.

Abstract

Stepwise modification of ovatodiolide revealed a prodrug, NMP-diepoxyovatodiolide, which can provide sustained release of an active compound, substantial metabolic stability and a unique accumulation profile in the liver. Besides, NMP-diepoxyovatodiolide demonstrated therapeutic benefits in an acute autoimmune hepatitis mouse model and a broad safety window. Therefore, NMP-diepoxyovatodiolide is a very promising candidate for further development of liver-related drugs.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Diterpenes / administration & dosage
  • Diterpenes / chemistry
  • Diterpenes / pharmacokinetics*
  • Hepatitis, Autoimmune / drug therapy*
  • Hepatitis, Autoimmune / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / chemistry
  • Microsomes, Liver / metabolism
  • Molecular Structure
  • Prodrugs / administration & dosage
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Diterpenes
  • Prodrugs
  • ovatodiolide