Synthesis of N-arylmethyl Substituted Indole Derivatives as New Antiplatelet Aggregation Agents

Document Type: Supplement (special issue)

Authors

1 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Iran, Vali Asr Ave. Niayesh Junction, Tehran, Iran.

2 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Iran.

3 Department of Pharmaceutics, School of Paharmacy, Shahid Beheshti University of Medical Sciences, PO Box: 14155-6153, Tehran, Iran.

4 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Iran, Vali Asr Ave, Niayesh Junction, Tehran, Iran

Abstract

A number of N-arylmethyl substituted indole derivatives have been synthesized and their effectiveness against ADP and arachidonic acid induced platelet aggregation in human plasma was determined. The desired compounds were synthesized by reacting the appropriate aniline derivative with isatin (or substituted isatin) to form the corresponding imine structures. The so formed compound was then activated using sodium hydride and reacted with the proper substituted benzyl halides. Among the tested compounds, derivatives 4a, 4c, 4d, 4f-i and 4k were the most potent compounds with satisfactory IC50 values (under 38.5 µM) for inhibition of platelet aggregation induced by arachidonic acid.
All indole derivatives without substitution on position 1 of the indole ring, exhibited either weaker activities or were not active at all.

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