Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506.
Bioorg Med Chem Lett
; 94: 129456, 2023 10 01.
Article
en En
| MEDLINE
| ID: mdl-37633618
ABSTRACT
Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Cápside
/
Proteínas de la Cápside
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article