Synthesis and Antiplatelet Activity Evaluation of a Group of Novel Ethyl Acetoacetate Phenylhydrazone Derivatives

Document Type: Research article

Authors

1 Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

A group of Novel phenylhydrazone derivatives of ethyl acetoacetate was synthesized and evaluated for their antiplatelet activities. Fourteen ethyl acetoacetate phenylhydrazone derivatives were synthesized using the diazonium salt of various aromatic primary amines with good yields and purity. The structure of the final compounds was confirmed and approved by spectroscopic techniques such as 1HNMR, FTIR, and ESI-Mass. We examined the antiplatelet activity of the derivatives against Arachidonic Acid (AA) and Adenosine Diphosphate (ADP) as platelet aggregation inducers. The final results indicated the acceptable potency for different derivatives. In this regard, the para-hydroxyphenylhydrazine derivative of ethyl acetoacetate has the best activity among all derivatives, both on AA and ADP pathways. It seems that the derivatives with electron-releasing substituents (hydroxyl, methoxy, and methyl group) have better inhibition activities against the aggregation induced by AA. In contrast, those with an electron-withdrawing group showed a significant decrease in their potency. Based on the results of this study, we would proceed with further assessments both in-vitro and in-vivo to get success in introducing some new antiplatelet agents to the clinic.

Graphical Abstract

Synthesis and Antiplatelet Activity Evaluation of a Group of Novel Ethyl Acetoacetate Phenylhydrazone Derivatives

Keywords