title: Synthesis of a water-soluble prodrug of entacapone.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, Finland. jukka.leppanen@uku.fi
authors.forename: J
authors.initials: J
authors.lastname: Leppänen
authors.forename: J
authors.initials: J
authors.lastname: Huuskonen
authors.forename: J
authors.initials: J
authors.lastname: Savolainen
authors.forename: T
authors.initials: T
authors.lastname: Nevalainen
authors.forename: H
authors.initials: H
authors.lastname: Taipale
authors.forename: J
authors.initials: J
authors.lastname: Vepsäläinen
authors.forename: J
authors.initials: J
authors.lastname: Gynther
authors.forename: T
authors.initials: T
authors.lastname: Järvinen
mesh_terms: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D009570:Nitriles; D011355:Prodrugs / Q000138:chemical synthesis*; D012995:Solubility
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D011355:Prodrugs; C071192:entacapone