Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand

摘要

src="http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/amclct/2017/amclct.2017.8.issue-9/acsmedchemlett.7b00245/20170908/images/medium/ml-2017-00245x_0003.gif">Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of Vγ9 Vδ2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC₅₀ of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC₅₀ in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus it should be a valuable tool for studies of T cell function. Furthermore, mixed aryl/acyloxyalkyl esters may represent a new class of phosphonate prodrugs with high efficacy.