N-Edited Guanine Isosteres.
J Org Chem
; 88(14): 9823-9834, 2023 07 21.
Article
em En
| MEDLINE
| ID: mdl-37431831
ABSTRACT
Guanine is one out of five endogenous nucleobases and of key interest in drug discovery and chemical biology. Hitherto, the synthesis of guanine derivatives involves lengthy multistep sequential synthesis of low overall diversity, resulting in the quest for innovation. Using a "single-atom skeletal editing" approach, we designed 2-aminoimidazo[2,1-f][1,2,4]triazin-4(3H)-one as a guanine isostere, conserving the biologically important HBA-HBD-HBD (HBA = hydrogen bond acceptor; HBD = hydrogen bond donor) substructure. We realized our design by a simple one-pot two-step method combining the Groebke-Blackburn-Bienaymé reaction (GBB-3CR) and a deprotection reaction to assemble the innovative guanine isosteres in moderate to good yields. Our innovative, diverse, short, and reliable multicomponent reaction synthesis will add to the toolbox of guanine isostere syntheses.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda