Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation

Levent S., ÇALIŞKAN B., Ciftci M., ÖZKAN Y., Yenicesu I., ÜNVER H., ...Daha Fazla

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.64, ss.42-53, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 64
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.ejmech.2013.03.048
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.42-53
  • Anahtar Kelimeler: Pyrazole, Carboxamide, Antiplatelet, Arachidonic acid, SELECTIVE COX-2 INHIBITORS, ANTIPLATELET ACTIVITY, BIOLOGICAL EVALUATION, AGENTS, RESISTANCE, THERAPY, PYRIDAZINES, PREVENTION, ASPIRIN, POTENT
  • Gazi Üniversitesi Adresli: Evet

Özet

Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.