Synthesis and biological evaluation of a new series of cinnamic acid amide derivatives as potent haemostatic agents containing a 2-aminothiazole substructure

摘要

Graphical abstract This study demonstrates the use of new compound N5 with potential characteristics for the development of drugs combining coagulant and platelet activities. Display Omitted Abstract Ten new cinnamic acid derivatives containing a 2-aminothiazole substructure were designed and synthesized. This series of compounds exhibited good thermostabilities as demonstrated by thermogravimetric analysis. In coagulation assays (prothrombin time, activated partial thromboplastin time and thrombin time) in vitro , most compounds demonstrated excellent activities to promote blood coagulation. Among the studied series, compounds N1 , N4 , N5 and W5 exhibited a significant coagulation activity. Further studies indicated that compound N5 (IC 50 =1.87μmol/L) displayed the most suitable efficacy of promoting platelet aggregation than the clinically used haemostatic drug etamsylate (IC 50 =46.22μmol/L). Furthermore, the relationship between the functional groups of the compounds and the corresponding blood coagulant activity was explored in this study.