Synthesis and in vitro anti-platelet aggregation activities of 2-methoxy-5-arylamido-N-(pyridin-3-yl-methyl)benzamides.

Abstract

In order to discover novel compounds with anti-platelet aggregation activities, a series of novel 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides (1a-n) were synthesized and their anti-platelet aggregation activities were evaluated by the turbidimetric method in response to the following agonists: adenosine diphosphate (ADP) (5 mM/L), arachidonic acid (AA) (20 µM/L), and collagen (1 mg/mL). Those synthesized compounds that have better in vitro activities were subjected to cell toxicity tests via cell counting kit-8 (CCK-8) assay. The biological evaluation revealed that compound 1a (IC50 : 0.21 µM/L) exhibited the highest anti-platelet aggregation activities when ADP was selected as an inducer, and compound 1b (IC50 : 0.23 µM/L) showed the best activities when AA was selected as inducer, and compound 1m (inhibition rate: 55.06%) had significant anti-platelet aggregation activities when collagen was selected as inducer among all target compounds. Moreover, the effect of cell toxicity exhibited that none of the compounds had obvious cell toxicity against L929 cells. Therefore, 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides have the potential to become a novel kind of anti-platelet drugs and deserve further study.