Bis[(para-methoxy)benzyl] phosphonate prodrugs with improved stability and enhanced cell penetration.

Bioorg Med Chem Lett

Department of Chemistry, Metabasis Therapeutics, Inc., 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.

Published: June 2007

A series of substituted bis[(para-methoxy)benzyl] (bisPMB) esters of 1-naphthalenemethylphosphonate (NMPA) were synthesized and evaluated as phosphonate prodrugs. BisPMB NMPA esters (4b and 4c) with significantly improved aqueous stability were identified that also resulted in increased intracellular levels of NMPA following prodrug incubation with primary rat hepatocytes.

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http://dx.doi.org/10.1016/j.bmcl.2007.03.089DOI Listing

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