Prodrug Strategy Extends the Use of Anti-HIV Sulfanylbenzamides for Application In Vivo.
ACS Pharmacol Transl Sci
; 7(1): 259-273, 2024 Jan 12.
Article
em En
| MEDLINE
| ID: mdl-38250006
ABSTRACT
Sulfanylbenzamide thioesters are molecules with anti-HIV activity that disrupt zinc coordination in the viral protein NCp7. These molecules are useful as topical microbicides; however, they are too unstable to be used systemically. In this article, a nitroimidazole prodrug was used to protect the sulfanylbenzamide to convey blood stability and oral bioavailability to the molecule. Studies on the molecule called nipamovir were performed to assess the rate of prodrug cleavage, antiviral activity, mechanism of metabolism, and in vivo pharmacokinetics in several different species. An efficient and inexpensive synthesis of nipamovir is also described. The results indicate that nipamovir could be further developed as a new type of drug to treat HIV infection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Pharmacol Transl Sci
Ano de publicação:
2024
Tipo de documento:
Article