Molecular design and evaluation of aza-polycyclic carbamoyl pyridones as HIV-1 integrase strand transfer inhibitors.
Bioorg Med Chem Lett
; 111: 129902, 2024 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-39059564
ABSTRACT
Integrase strand transfer inhibitors (INSTIs) are the most prescribed anchor drug in antiretroviral therapy. Today, there is an increasing need for long-acting treatment of HIV-1 infection. Improving drug pharmacokinetics and anti-HIV-1 activity are key to developing more robust inhibitors suitable for long-acting formulations, but 2nd-generation INSTIs have chiral centers, making it difficult to conduct further exploration. In this study, we designed aza-tricyclic and aza-bicyclic carbamoyl pyridone scaffolds which are devoid of the problematic hemiaminal stereocenter present in dolutegravir (DTG). This scaffold hopping made it easy to introduce several substituents, and evolving structure-activity studies using these scaffolds resulted in several leads with promising properties.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Desenho de Fármacos
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HIV-1
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Inibidores de Integrase de HIV
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Integrase de HIV
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article