Development of tenofovir monobenzyl ester phosphonoamidate prodrugs with improved anti-hepatitis B virus activity and intrahepatic tenofovir enrichment
Copyright © 2024 Elsevier Ltd. All rights reserved..
Various tenofovir (TFV) prodrugs have been developed by introducing masking groups to the hydroxyls of the monophosphonate group to enhance intestinal absorption efficiency and therapeutic effects. However, the reported TFV prodrugs have drawbacks such as low bioavailability, systemic toxicity caused by their breakdown in non-targeted tissues, and potential low intracellular conversion efficiency. In the present study, we developed a class of TFV monobenzyl ester phosphonoamidate prodrugs without substitutions on the benzene ring. Compared with previous TFV prodrugs, compounds 3a and 3b developed in the present study showed higher anti-hepatitis B virus activity, stronger stability and higher levels of intrahepatic enrichment of the metabolic product (TFV), indicating the potential of these compounds as novel prodrugs with high efficiency and low systemic toxicity for the treatment of hepatitis B.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:99 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 99(2024) vom: 01. Feb., Seite 117607 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Xizheng [VerfasserIn] |
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| Links: |
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| Themen: |
99YXE507IL |
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| Anmerkungen: |
Date Completed 06.02.2024 Date Revised 06.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2024.117607 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Various tenofovir (TFV) prodrugs have been developed by introducing masking groups to the hydroxyls of the monophosphonate group to enhance intestinal absorption efficiency and therapeutic effects. However, the reported TFV prodrugs have drawbacks such as low bioavailability, systemic toxicity caused by their breakdown in non-targeted tissues, and potential low intracellular conversion efficiency. In the present study, we developed a class of TFV monobenzyl ester phosphonoamidate prodrugs without substitutions on the benzene ring. Compared with previous TFV prodrugs, compounds 3a and 3b developed in the present study showed higher anti-hepatitis B virus activity, stronger stability and higher levels of intrahepatic enrichment of the metabolic product (TFV), indicating the potential of these compounds as novel prodrugs with high efficiency and low systemic toxicity for the treatment of hepatitis B | ||
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| 700 | 1 | |a Cai, Jinyong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Hai |e verfasserin |4 aut | |
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