Novel N‐Substituted ((1H‐indol‐3‐yl)methylene)benzohydrazides and ((1H‐indol‐3‐yl)methylene)‐2‐phenylhydrazines: Synthesis and Antiplatelet Aggregation Activity

Abstract

Based on our previous studies on antiplatelet hydrazone derivatives, some new indole‐based derivatives were designed and synthesized as potential antiplatelet agents. Synthesis of the derivatives was accomplished by substitution at the N – 1 position of indole‐3‐carboxaldehyde and reacting the resulting intermediates with either phenylhydrazine of benzoylhydrazide. The structure of the synthesized compounds was confirmed by different spectral methods such as mass spectrometry, 1H‐NMR, and IR spectroscopy. The derivatives were tested for their ability to inhibit human platelet aggregation, where arachidonic acid (AA), adenosine diphosphate ADP, and collagen were used as aggregation inducers. Compounds (2a–2f) showed considerable activity against AA‐induced platelet aggregation. Among them, compounds 2a, 2b, and 2f were the most potent derivatives with IC50 values comparable to that of aspirin as standard drug. Analysis of structure–activity relationship shows that with increased bulk of the substituents at indole N – 1, the antiplatelet activity is reduced, thus suggesting that steric hindrance at this position plays a major role in the activity of the tested compounds.