Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives bearing 1,3-thiazole moiety as novel anti-inflammatory EGFR inhibitors with cardiac safety profile

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

“…Compounds 56a , 56b , and 56c showed in vivo anti-inflammatory activity up to 90%, 94%, and 86% of meloxicam, respectively, after a 4 h interval. Moreover, the compounds showed higher gastric safety profiles than meloxicam 71 .…”

“…Abdel-Aziz et al. 71 synthesised a novel series of pyrimidine-5-carbonitrile derivatives and evaluated their anti-inflammatory activity against COX-1/COX-2 activity. Results indicated that compounds 56a , 56b , and 56c were potent and selective COX-2 inhibitors (IC 50 =1.03–1.71 µM) compared to celecoxib (IC 50 =0.88 µM).…”

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

“…Later, Abdel-Aziz et al. 44 synthesized a few novel anti-inflammatory EGFR inhibitors with cardiac and gastric safety profiles. Chemically, these compounds were formed with pyrimidine-5-carbonitrile hybrids with 2-amino-4-aryl-1,3-thiazole through an acetamide group linker.…”

New N-Substituted-1,2,4-triazole Derivatives of Pyrrolo[3,4-d]pyridazinone with Significant Anti-Inflammatory Activity—Design, Synthesis and Complementary In Vitro, Computational and Spectroscopic Studies

“…New drug candidates with potential application in the treatment of various inflammatory disorders can be received either through the structural alteration of already known NSAIDs, such as Diclofenac [ 18 ], Naproxen [ 19 ], Celecoxib [ 20 ], Ibuprofen [ 21 ], or by developing fully novel classes of cyclooxygenase inhibitors. When considering the design of new anti-inflammatory agents, one of the most popular and effective synthetic approaches in contemporary medicinal chemistry relies on replacing the free carboxylic group with different bioisosteric five-membered heterocyclic rings, such as 1,3,4-oxadiazole [ 18 , 19 , 20 , 21 , 22 ], 1,3-thiazole [ 23 , 24 , 25 ], pyrazole [ 26 , 27 ] or 1,2,4-triazole [ 28 , 29 , 30 , 31 , 32 , 33 ]. According to the leading investigations, such a strategy can be successfully applied to modify widespread used NSAIDs and other promising compounds not introduced in the market yet.…”

“…It also acts as a valuable building block used in the design and synthesis of promising analgesic and anti-inflammatory agents, especially those with a good affinity towards an inducible COX-2 isoform [ 28 , 30 , 31 , 32 ]. Needless to say, different five-membered heterocycles serve as the structural core of the previously mentioned selective COX-2 inhibitors—COXIBs [ 17 , 20 , 25 ]. Considering that the binding pocket of COX-2 isoenzyme is bigger than that of COX-1 [ 6 , 7 , 8 , 9 , 10 ], we expect that the presence of expanded 4-substituted-1,2,4-triazole residues will enhance the COX-2 selectivity of titled compounds.…”