Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors

Bioorg Med Chem Lett. 2024 Feb 1;99:129610. doi: 10.1016/j.bmcl.2024.129610. Epub 2024 Jan 9.ABSTRACTA 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.PMID:38211702 | DOI:10.1016/j.bmcl.2024.129610

Source: Bioorganic and Medicinal Chemistry Letters - January 11, 2024 Category: Chemistry Authors: Yanshi Wang Jianglin Yuan Sida Yan Peng Liu Zhichao Zheng Shijun Zhang Fancui Meng Wei Liu Changjiang Huang Qunchao Wei Source Type: research