Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4-triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents^*

Abstract

The aim of this research work was to investigate a series of novel 5,6-diaryl-1,2,4-triazines (3a–3q) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by in vitro, ex vivo and in vivo methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (3l) and (3m) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent in vitro than aspirin; six of them were found to be prominent in ex vivo assays and one compound (3d) was found to have the most promising antithrombotic profile in vivo. Moreover, compound (3d) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (3d) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity.

• 1,2,4-Triazines
• antithrombotic agents
• antiplatelet agents
• aspirin
• green synthesis
• molecular docking

Declaration of interest

We thank All India Council for Technical Education (AICTE), New Delhi, India for National Doctoral Fellowship to RST [File No. 1–10/RID/NDF/PG/36/2009–2010]. The authors also thank the DST-PURSE Single Crystal X-Ray Diffraction Facility at the Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara for single crystal X-ray crystallographic studies.

The authors declare that they have no conflicts of interest to disclose.

Supplementary material available online

Supplementary Figure S1

Notes

* This article is dedicated to fond memories of Late Prof. (Mrs.) Rajani Giridhar.