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Design, Synthesis, and Anti-HBV Activity of New Bis(l-amino acid) Ester Tenofovir Prodrugs.

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 ?M) than the parent drug TFV. The most active compound 11 (IC₅₀: 0.71 ?M), a bis(l-valine) ester prodrug of TFV, was found to have obviously greater AUC_0-?, C _max, 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.

SUBMITTER: Wang A

PROVIDER: S-EPMC6580537 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Anti-HBV Activity of New Bis(l-amino acid) Ester Tenofovir Prodrugs.

Wang Apeng A Wu Shuo S Tao Zeyu Z Li Xiaoning X Lv Kai K Ma Chao C Li Yuhuan Y Li Linhu L Liu Mingliang M

ACS medicinal chemistry letters 20190516 6

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-∞, C max, and F% than tenofovir disoproxil fumarate (T ...[more]

PMID: 31223460

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