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Molecules 2015, 20(8), 15287-15303;

Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors

Chemistry Department, Faculty of Science, Fayoum University, El-Fayoum 63551, Egypt
Department of Chemistry, Faculty of Science, Bani Suef University, Bani Suef 62111, Egypt
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
Research Unit, Saco Pharm. Co., 6th of October City 68330, Egypt
Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 22 July 2015 / Revised: 2 August 2015 / Accepted: 6 August 2015 / Published: 21 August 2015
(This article belongs to the Section Organic Chemistry)
Full-Text   |   PDF [1444 KB, uploaded 21 August 2015]   |  


The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds. View Full-Text
Keywords: aminopyrazolopyridine; anti-inflammatory; cyclooxygenase; hydrazonyl halides; selective inhibitors aminopyrazolopyridine; anti-inflammatory; cyclooxygenase; hydrazonyl halides; selective inhibitors

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Badrey, M.G.; Abdel-Aziz, H.M.; Gomha, S.M.; Abdalla, M.M.; Mayhoub, A.S. Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors. Molecules 2015, 20, 15287-15303.

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