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

…, BG Ugarkar, JE Gómez-Galeno…

Index: Boyer, Serge H.; Sun, Zhili; Jiang, Hongjian; Esterbrook, Julie; Gomez-Galeno, Jorge E.; Craigo, William; Reddy, K. Raja; Ugarkar, Bheemarao G.; MacKenna, Deidre A.; Erion, Mark D. Journal of Medicinal Chemistry, 2006 , vol. 49, # 26 p. 7711 - 7720

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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, ...