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Keywords = aminopyrazolopyridine

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17 pages, 1444 KiB  
Article
Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors
by Mohamed G. Badrey, Hassan M. Abdel-Aziz, Sobhi M. Gomha, Mohamed M. Abdalla and Abdelrahman S. Mayhoub
Molecules 2015, 20(8), 15287-15303; https://doi.org/10.3390/molecules200815287 - 21 Aug 2015
Cited by 26 | Viewed by 8027
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, [...] Read more.
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. Full article
(This article belongs to the Section Organic Chemistry)
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