Novel amides and esters prodrugs of olmesartan: Synthesis, bioconversion, and pharmacokinetic evaluation

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5895-9. doi: 10.1016/j.bmcl.2010.07.089. Epub 2010 Jul 25.

Abstract

Synthesis of novel amides and esters prodrugs of olmesartan is described. Their in vitro stability in rat plasma was tested. The results showed that the ester derivative IIa with n-octyl substituted dioxolone moiety was rapidly converted into olmesartan within 30 min. The pharmacokinetic parameters of IIa were studied and compared with those of olmesartan medoxomil. Compound IIa is proposed to be a promising prodrug of olmesartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amides / chemistry*
  • Animals
  • Esters
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacokinetics
  • Male
  • Olmesartan Medoxomil
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / chemistry
  • Tetrazoles / pharmacokinetics

Substances

  • Amides
  • Esters
  • Imidazoles
  • Prodrugs
  • Tetrazoles
  • Olmesartan Medoxomil
  • olmesartan