Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability
Acta Pharmaceutica Sinica B
; (6): 810-822, 2021.
Article
em En
| WPRIM
| ID: wpr-881170
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WPRO
ABSTRACT
Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (
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Índice:
WPRIM
Idioma:
En
Revista:
Acta Pharmaceutica Sinica B
Ano de publicação:
2021
Tipo de documento:
Article