Synthesis of acyloxymethyl ester prodrugs of the transferable protein farnesyl transferase substrate farnesyl methylenediphosphonate

Bioorganic & Medicinal Chemistry Letters
Jerry M TroutmanH Peter Spielmann

Abstract

Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs.

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Citations

Apr 1, 2011·Drug Development and Industrial Pharmacy·Ting-Li LuTao Chen
Oct 28, 2015·Chembiochem : a European Journal of Chemical Biology·Andrew J WiemerDavid F Wiemer
Oct 13, 2006·Angewandte Chemie·Luc BrunsveldHerbert Waldmann
Aug 31, 2019·Future Medicinal Chemistry·Kenneth M Heidel, Cynthia S Dowd
Dec 23, 2019·RSC Medicinal Chemistry·Pimyupa ManaswiyoungkulPatrick T Gunning

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