ABSTRACT

Objective: Design and synthesize a new Aminoacetylenic-4,4-dimethylglutarimide derivatives and investigate their selective inhibitory activity to COXs. Methods: Aminoacetylenic-4,4-dimethylglutarimide derivatives were synthesized by alkylation of 4,4-dimethylglutarimide with propargyl bromide afforded 4,4-dimethyl-1-(prop- 2-yn-1-yl)piperidine-2,6-dione. The alkylated4,4-dimethylglutarimide was subjected to Mannich reaction afforded the desired Aminoacetylenic-4,4-dimethylglutarimides (ZS-1 to ZS-8). The elemental analysis was indicated by the Euro EA elemental analyzer (Jordan University) and chemical structures were investigated via IR, 1H-NMR, 13C-NMR, DSC (Star system, Switzerland) with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d6 as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes. Results: The IR, 1H-NMR, 13C-NMR, DSC and elemental analysis were consistent with the assigned structures. The design of these compounds as COXs inhibitors were based on the rationalization of the important ?–interaction or aromaticity criteria that provide effective inhibitory with COXs–enzymes. Conclusion: Requirement of aromaticity in binding affinity to COXs enzymes was very essential. Keywords: Aminoacetylenic, 4,4-Dimethylglutarimide, Molecular modelling, Cyclooxygenase inhibitors, Anti-inflammatory

https://ijbpas.com/pdf/2019/September/MS_IJBPAS_2019_4800.pdf

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https://doi.org/10.31032/IJBPAS/2019/8.9.4800