Synthesis, oral bioavailability determination, and in vitro evaluation of prodrugs of the antiviral agent 9-[2-(phosphonomethoxy) ethyl] adenine (PMEA)

…, J Russell, MJM Hitchcock, V Whiterock…

Index: Starrett, John E.; Tortolani, David R.; Russell, John; Hitchcock, Michael J. M.; Whiterock, Valerie; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 12 p. 1857 - 1864

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Citation Number: 185

Abstract

A series of phosphonate prodrugs were evaluated in an attempt to increase the oral bioavailability of the anti-HIV agent 9-[2-(phosphonomethoxy) ethyll adenine (PMEA; 1). The majority of the bis (alky1 ester) and bis (alky1 amide) prodrugs were prepared by alcohol or amine displacement of dichlorophosphonate 2. Basic hydrolysis of the bis (esters) or bis (amides) provided the corresponding monoesters or monoamides. Synthesis of bis [( ...