Abstract:
:A series of bis(l-amino acid) ester prodrugs of tenofovir (TFV) were designed and synthesized as new anti-HBV agents in this work. Four compounds 11, 12a, 12d, and 13b displayed better anti-HBV activity (IC50: 0.71-4.22 μM) than the parent drug TFV. The most active compound 11 (IC50: 0.71 μM), a bis(l-valine) ester prodrug of TFV, was found to have obviously greater AUC0-∞,Cmax, and F% than tenofovir disoproxil fumarate (TDF), and potent in vivo efficacy which is not inferior to TDF in a duck HBV (DHBV) model and a HBV DNA hydrodynamic mouse model, and it may serve as a promising lead compound for further anti-HBV drug discovery.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Wang A,Wu S,Tao Z,Li X,Lv K,Ma C,Li Y,Li L,Liu Mdoi
10.1021/acsmedchemlett.9b00184subject
Has Abstractpub_date
2019-05-16 00:00:00pages
991-995issue
6issn
1948-5875journal_volume
10pub_type
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