Pradefovir: a prodrug that targets adefovir to the liver for the treatment of hepatitis B

…, BG Ugarkar, JE Gómez-Galeno, J DaRe…

Index: Reddy, K. Raja; Matelich, Michael C.; Ugarkar, Bheemarao G.; Gomez-Galeno, Jorge E.; DaRe, Jay; Ollis, Kristin; Sun, Zhili; Craigo, William; Colby, Timothy J.; Fujitaki, James M.; Boyer, Serge H.; Van Poelje, Paul D.; Erion, Mark D. Journal of Medicinal Chemistry, 2008 , vol. 51, # 3 p. 666 - 676

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Citation Number: 51

Abstract

Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1, 3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, ...