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

ID: ALA4396904

Journal: ACS Med Chem Lett

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

Authors: Wang A, Wu S, Tao Z, Li X, Lv K, Ma C, Li Y, Li L, Liu M.

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 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.

CiteXplore: 31223460

DOI: 10.1021/acsmedchemlett.9b00184

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