Design, synthesis and preliminary pharmacological evaluation of new possible non-steroidal anti-inflammatory agents having the 5-(methylsulfonyl)-1,2,4-triazole-3-amine pharmacophore

Tariq Hussien Mousa
1; Amer N. Elias
2

Abstract

Design, synthesis and preliminary pharmacological evaluation of new possible non-steroidal anti-inflammatory agents having the 5-(methylsulfonyl)-1,2,4-triazole-3-amine pharmacophore

Author(s): Tariq Hussien Mousa 1 and Amer N. Elias 2*

Design and synthesizenew derivatives of well-known classical NSAIDs with an increased bulkiness and ex pected selectivity towards the COX-2 enzyme, while being d evoid of ulcerogenic effects. The target compounds were synthesized by conjugating an amino derivatives [5- (methylsulfonyl)-4H-1,2,4-triazol-3-amine] as an am ide with the carboxyl group of a number of well-known NSAIDs. Sy nthetic procedures have been successfully developed for the generation of the target compounds (T 1 -T 4 ). The structure of the synthesized derivatives has been characterized by elemental microanalysis (CHN), FTIR Spectroscopy, a nd other physicochemical properties. In vivo acute anti- inflammatory activity of the final target compounds (T 1 -T 4 ) was evaluated in rats using the egg-white induced edema model of inflammation in a dose equivalent to (3 mg /Kg) of Diclofenac Sodium. All tested compounds pro duced a significant reduction in paw edema with a continued effect till the end of the experiment in respect t o the effect of propylene glycol 50% v/v (control group). Moreover, target compound T 3 exhibited superior anti-inflammatory activity compared to Diclofenac Sodium at times 180 -300 minutes with the same onset of action. Theinco rporated 5- (methylsulfonyl)-4H-1,2,4-triazol-3-aminePharma-cop hore into the final target compounds has maintained and even synergizedthe anti-inflammatory activity of the cho sen classical NSAIDs and this may be due to an incr eased selectivity towards the COX-2 enzyme, a factor whic h need to be confirmed in future by assessing COX-1 :COX-2 inhibitory ratios.

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