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
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridones
/
Drug Design
/
HIV-1
/
HIV Integrase Inhibitors
/
HIV Integrase
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Document type:
Article
Country of publication: