Synthesis, pharmacological evaluation, and mechanistic study of adefovir mixed phosphonate derivatives bearing cholic acid and l-amino acid moieties for the treatment of HBV.
Adefovir
Hepatitis B virus
Hepatotrophic properties
Nephrotoxicity
Organic anion transporter 1
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
30
05
2019
revised:
27
06
2019
accepted:
06
07
2019
pubmed:
16
7
2019
medline:
17
9
2020
entrez:
15
7
2019
Statut:
ppublish
Résumé
The deficiency of nucleos(t)ide analogues (NAs) as anti-hepatitis B virus (HBV) drugs in clinical use is attributable to their insufficient enrichment in liver and non-target organ toxicity. We aimed to develop potent anti-HBV adefovir derivatives with hepatotrophic properties and reduced nephrotoxicity. A series of adefovir mono l-amino acids, mono cholic acid-drug conjugates were designed and synthesized, and their antiviral activity and uptake in rat primary hepatocytes and Na
Identifiants
pubmed: 31301948
pii: S0968-0896(19)30903-4
doi: 10.1016/j.bmc.2019.07.012
pii:
doi:
Substances chimiques
Antiviral Agents
0
Organophosphonates
0
adefovir
6GQP90I798
Cholic Acid
G1JO7801AE
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3707-3721Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.