Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors.
Bioorg Med Chem Lett
; 99: 129610, 2024 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-38211702
ABSTRACT
A series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of P1, P1 prime and P2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. 14c demonstrated excellent in-vitro potency (FXIa IC50 15 nM, 2 x aPTT 6.8 µM) and good in-vivo efficacy (prolonged in-vivo aPTT by more than 1-fold but not PT). Moreover, the pharmacokinetics property of 14c were evaluated following intravenous administration in rats, which indicated that 14c probably will be a clinical candidate for intravenous administration.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Blood Coagulation
/
Factor XIa
Limits:
Animals
Language:
En
Year:
2024
Type:
Article