Design, synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors

作者：El Sayed Mardia T^*; El Sharief Marwa A M Sh^*; Zarie Eman S; Morsy Nesrin M; Elsheakh Ahmed R; Voronkov Andrey; Berishvili Vladimir; Hassan Ghada S^*

来源：Bioorganic & Medicinal Chemistry Letters, 2018, 28(5): 952-957.

DOI：10.1016/j.bmcl.2018.01.043

• Synthesis
• Antipyrine
• Pyrazolone derivatives
• COX-1
• COX-2
• Anti-inflammatory activity
• Molecular modeling

As a part of a directed program for development of new active agents, novel heterocyclic derivatives with antipyrine and pyrazolone moieties -incorporated in- have been designed and synthesized. Starting with 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivative 2a,b novel Mannich bases derivatives have been synthesized and biologically evaluated for their anti-inflammatory activity. Furthermore, the activity of such compounds has been tested interestingly as COX-1 and COX-2 inhibitors. Structure elucidation of the synthesized compounds was attained by the use of elemental analysis, IR, H-1 NMR, C-13 NMR, and Mass spectrometry techniques. Compounds 3b, 3d and 4b represent the high % inhibition values for both COX-1 and COX-2. On the other hand, compound 8 showed little selectivity against COX-2 while compound 10 showed good selectivity against COX-1 only. Structure activity relationship has been discussed and the results were confirmed by molecular docking calculations.

• 出版日期2018-3-1