Design, synthesis and antiplatelet activity evaluation of novel quinoxaline antagonists of protease activated receptor 4 (PAR4)
10.16438/j.0513-4870.2021-1236
- VernacularTitle:新型喹喔啉类蛋白酶激活受体4 (PAR4) 拮抗剂的设计、合成及抗血小板活性研究
- Author:
Rou-jie XIE
;
Shang-de LIU
;
Duo YUAN
;
Shan-shan LI
;
Xiong ZHU
- Publication Type:Research Article
- Keywords:
quinoxaline;
protease activated receptor 4 antagonist;
selectivity;
antiplatelet activity
- From:
Acta Pharmaceutica Sinica
2022;57(3):731-740
- CountryChina
- Language:Chinese
-
Abstract:
Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.
