Synthesis of a Complex and Highly Potent PCSK9 Inhibitor.
Org Lett
; 25(27): 5001-5005, 2023 07 14.
Article
em En
| MEDLINE
| ID: mdl-37382389
ABSTRACT
The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2, followed by stepwise installation of Eastern 3, Southern 4, and Western 5 fragments, provided macrocyclic precursor 19. This intermediate was cross-linked via an intramolecular azide-alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1. Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pró-Proteína Convertase 9
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article