Synthesis of a water-soluble prodrug of entacapone

Bioorg Med Chem Lett. 2000 Sep 4;10(17):1967-9. doi: 10.1016/s0960-894x(00)00384-x.

Abstract

Entacapone was reacted with phosphorous oxychloride in dry pyridine to yield a phosphate ester. The phosphate promoiety increased aqueous solubility of the parent drug by more than 1700- and 20-fold at pH 1.2 and 7.4, respectively. The phosphate ester provides adequate stability (t(1/2) = 2227 h; pH 7.4) towards chemical hydrolysis, and allowed for release of the parent drug via enzymatic hydrolysis in liver homogenate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / chemical synthesis*
  • Enzyme Inhibitors / chemical synthesis*
  • Hydrogen-Ion Concentration
  • Nitriles
  • Prodrugs / chemical synthesis*
  • Solubility

Substances

  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Nitriles
  • Prodrugs
  • entacapone