Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Taç Sok. No:3, Etiler, Yenimahalle, Ankara 06330, Turkey.
Eur J Med Chem. 2013 Jun;64:42-53. doi: 10.1016/j.ejmech.2013.03.048. Epub 2013 Apr 6.
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-aggregatory 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.
抗血小板药物是一种有前途的治疗方法，可以干预动脉血栓形成中的血小板聚集，尤其是在心肌梗死和缺血性中风中。在这里，我们描述了基于 1,5-二芳基吡唑-3-甲酰胺支架的具有强血小板聚集抑制活性的化合物的合成和构效关系。该系列的类似物表现出针对由 Born 比浊法测量的花生四烯酸诱导的血小板聚集的强抗聚集活性。用小碱性胺（7、8、50、51、61、62）获得的 1,5-二芳基吡唑-3-甲酰胺显示出最强的活性，IC50 值在低纳摩尔范围内（5.7-83 nM）。基于它们在细胞环境中的高效力，这些简单的吡唑衍生物可能具有在设计用于干预心血管疾病的更有效化合物方面的潜力。
