Leppänen J, Huuskonen J, Savolainen J, Nevalainen T, Taipale H, Vepsäläinen J, Gynther J, Järvinen T
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Bioorg Med Chem Lett. 2000 Sep 4;10(17):1967-9. doi: 10.1016/s0960-894x(00)00384-x.
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.
