Identification of novel 3-aryl-1-aminoisoquinolines-based KRASG12C inhibitors: Rational drug design and expedient construction by CH functionalization/annulation.
Bioorg Chem
; 142: 106954, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37948926
ABSTRACT
Developing a synthetic methodology to expediently construct a specific drug scaffold with the desired biological activity remains challenging. Herein, we describe a work on rational application of a synthetic methodology in the synthesis of KRASG12C inhibitors. Novel KRASG12C inhibitors were initially designed with 1-amino-3-aryl isoquinoline scaffold using structure-based drug design strategy. A ruthenium-catalyzed direct monoCH functionalization/annulation cascade reaction of amidines and sulfoxonium ylides was then developed with high versatility of substrates and good tolerance for polar functional groups. By using this reaction, the target compounds 1-amino-3-aryl isoquinolines were facilely prepared. Further in vitro tests led to identification of two novel lead compounds with KRASG12C inhibitory activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas p21(ras)
/
Isoquinolinas
Idioma:
En
Revista:
Bioorg Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China