Your browser doesn't support javascript.
loading
Identification of novel 3-aryl-1-aminoisoquinolines-based KRASG12C inhibitors: Rational drug design and expedient construction by CH functionalization/annulation.
Gong, Zirong; Zhao, Yu; Xu, Buyi; Yang, Zhou; Ren, Boquan; Yang, Han; Zeng, Chengfu; Chen, Renqiang; Xu, Yan-Jun; Li, Qing.
Afiliação
  • Gong Z; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Zhao Y; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Xu B; National Anti-drug Laboratory Sichuan Regional Center, Chengdu, Sichuan, 610206, China.
  • Yang Z; National Anti-drug Laboratory Sichuan Regional Center, Chengdu, Sichuan, 610206, China.
  • Ren B; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Yang H; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Zeng C; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Chen R; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China.
  • Xu YJ; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China. Electronic address: xuyj@sicnu.edu.cn.
  • Li Q; College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610066, China. Electronic address: qingli2021@sicnu.edu.cn.
Bioorg Chem ; 142: 106954, 2024 01.
Article em 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.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas p21(ras) / Isoquinolinas Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas p21(ras) / Isoquinolinas Idioma: En Ano de publicação: 2024 Tipo de documento: Article