Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity

  • Eur J Med Chem. 2020 Dec 15;208:112767. doi: 10.1016/j.ejmech.2020.112767.
Eric Goffin  1 ,  Nicolas Jacques  2 ,  Lucia Musumeci  2 ,  Alain Nchimi  2 ,  Cécile Oury  2 ,  Patrizio Lancellotti  2 ,  Bernard Pirotte  3
Affiliations
  • 1. Laboratory of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU Sart Tilman, Liège, Belgium.
  • 2. Laboratory of Cardiology, GIGA Cardiovascular Sciences, University of Liège, Department of Cardiology, University of Liège Hospital, CHU Sart Tilman, Liège, Belgium.
  • 3. Laboratory of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU Sart Tilman, Liège, Belgium. Electronic address: [email protected].
PMID: 32916314 DOI: 10.1016/j.ejmech.2020.112767
Abstract

Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and Antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro Antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the Antibacterial activity, supporting the view that the two activities were not necessarily linked.

Keywords
1,2,3-triazolo[4,5-d]pyrimidines; 8-Azapurines; Antibiotics; Antiplatelet agents; Ticagrelor.
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