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Amidate Prodrugs of Deoxythreosyl Nucleoside Phosphonates as Dual Inhibitors of HIV and HBV Replication.

Abstract：

:The synthesis of four l-2'-deoxy-threose nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine, and guanosine has been performed. Especially the adenine containing analogue (PMDTA) was endowed with potent antiviral activity displaying an EC50 of 4.69 μM against HIV-1 and an EC50 value of 0.5 μM against HBV, whereas completely lacking cytotoxicity. The synthesis of a number of phosphonomonoamidate and phosphonobisamidate prodrugs of PMDTA led to a boost in antiviral potency. The most potent congeners were a l-aspartic acid diisoamyl ester phenoxy prodrug and a l-phenylalanine propyl ester phosphonobisamidate prodrug that both display anti-HIV and anti-HBV activities in the low nanomolar range and selectivity indexes of more than 300.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Liu C,Dumbre SG,Pannecouque C,Huang C,Ptak RG,Murray MG,De Jonghe S,Herdewijn P

doi

10.1021/acs.jmedchem.6b01260

subject

Has Abstract

pub_date

2016-10-27 00:00:00

pages

9513-9531

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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