Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors,Bioorganic & Medicinal Chemistry Letters

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Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2024-01-09 , DOI: 10.1016/j.bmcl.2024.129610
Yanshi Wang ₁ , Jianglin Yuan ₁ , Sida Yan ₁ , Peng Liu ₁ , Zhichao Zheng ₁ , Shijun Zhang ₁ , Fancui Meng ₁ , Wei Liu ₁ , Changjiang Huang ₁ , Qunchao Wei ₁

Affiliation

A series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of 1, 1 prime and 2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. demonstrated excellent in-vitro potency (FXIa IC: 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 were evaluated following intravenous administration in rats, which indicated that probably will be a clinical candidate for intravenous administration.

中文翻译：

新型 FXIa 抑制剂 6-氯-喹啉-2-酮衍生物的设计、合成和生物学评价

通过探索1、1素和2素基团，设计并合成了一系列作为FXIa抑制剂的6-氯-喹啉-2-酮衍生物。评估每种化合物对 FXIa 的抑制作用，并在凝血测定中评估其中一些化合物。表现出优异的体外效力（FXIa IC：15 nM，2 x aPTT：6.8 μM）和良好的体内功效（体内 aPTT 延长超过 1 倍，但不延长 PT）。此外，在大鼠静脉内给药后评估了其药代动力学特性，这表明它可能成为静脉内给药的临床候选者。

更新日期：2024-01-09

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