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

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

  • Bioorg Med Chem Lett. 2017 Sep 15;27(18):4506-4511. doi: 10.1016/j.bmcl.2017.07.058.
Wenqian Nong 1,  Anran Zhao 2,  Jinrui Wei 3,  Xiao Lin 4,  Lisheng Wang 1,  Cuiwu Lin 5
Affiliations

Affiliations

  • 1 Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development, School of Chemistry & Chemical Engineer in Guangxi University, Nanning 530004, China.
  • 2 Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, United States.
  • 3 Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China.
  • 4 Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
  • 5 Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development, School of Chemistry & Chemical Engineer in Guangxi University, Nanning 530004, China. Electronic address: [email protected].
PMID: 28844387 DOI: 10.1016/j.bmcl.2017.07.058
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 (IC50=1.87μmol/L) displayed the most suitable efficacy of promoting platelet aggregation than the clinically used haemostatic drug etamsylate (IC50=46.22μmol/L). Furthermore, the relationship between the functional groups of the compounds and the corresponding blood coagulant activity was explored in this study.

Keywords

2-Aminothiazole; Cinnamic acid derivatives; Coagulant activity; Crystal structure; Platelet aggregation.

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