Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 InhibitorsReport as inadecuate




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Chemistry Department, Faculty of Science, Fayoum University, El-Fayoum 63551, Egypt

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Department of Chemistry, Faculty of Science, Bani Suef University, Bani Suef 62111, Egypt

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Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

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Research Unit, Saco Pharm. Co., 6th of October City 68330, Egypt

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Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt





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Author to whom correspondence should be addressed.



Academic Editor: Jean Jacques Vanden Eynde

Abstract 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 rings afforded less active compounds. View Full-Text

Keywords: aminopyrazolopyridine; anti-inflammatory; cyclooxygenase; hydrazonyl halides; selective inhibitors aminopyrazolopyridine; anti-inflammatory; cyclooxygenase; hydrazonyl halides; selective inhibitors





Author: Mohamed G. Badrey 1, Hassan M. Abdel-Aziz 2, Sobhi M. Gomha 3,* , Mohamed M. Abdalla 4 and Abdelrahman S. Mayhoub 5

Source: http://mdpi.com/



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