Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile

Plants as Sources of Anti-Inflammatory Agents

“…A derivative of celecoxib based a benzo[b]furan moiety was reported to demonstrate selective activity against COX-2. Besides, new molecules containing rhodanine and benzofuran scaffolds were designed, synthesized, and reported to exhibit dual COX-2, and 5-LOX inhibitory potential [ 39 , 40 ]. A recent patent survey reported a review focused on benzofuran inhibitors [ 41 , 42 ].…”

Development of pyrazole derivatives in the management of inflammation

“…The pyrazole derivative–enzyme interaction has been evaluated using molecular docking. The result of this assessment provides the affinity of designed compounds and contributes to the detection of acceptable inhibitors of COX‐2 ( 15 ; 17 ; 23–32 ; 34–37 ; 39 ; 51 ; 58 ; 60 ; 61 ; 69–72 ; 74 ; 85–87 ) [18,26,27–34,35–39] and 5‐LOX ( 46 ; 63 ; 82–84 ) [40–42] catalytic activity. The energy score of docked derivatives appears related to the degree of enzyme inhibition and selectivity.…”

“…Compound 32 with better enzyme interaction ( E score = −15.00 Kcal/mol) possess more H‐bond features (Arg499, Ser516, Gln178, and Tyr341) than other derivatives and celecoxib ( 5 ) [26]. The amino acid residues Phe504, Tyr371, Tyr355, Ser516, His372 Lys197, Trp373, Leu338, His337, and His175 are additional sites accessible to pyrazole derivatives [32–36]. The compound 74 and some NSAIDs interact with the catalytic (Ser530), ligand‐stabilizing (Arg120), and cavity‐forming (Ile523 and Ala527) residues of COX‐1 that are related to their potency [39].…”

“…Several pyrazole derivatives exhibited higher selectivity in the inhibition of the ovine [16,26,32–34,44,46–50] or human [35–37,51–55] recombinant COX‐2. Like COX‐2, the inhibition of LOX is important for the development of nonulcerogenic and cardiotoxic drugs [56–58].…”

Crystal structure and Hirshfeld surface analysis of N-{2-[(E)-(4-methylbenzylidene)amino]phenyl}-2-(5-methyl-1-H-pyrazol-3-yl)acetamide hemihydrate

“…Pyrazole derivatives are biologically active heterocyclic compounds (Karrouchi et al, 2018). This compound class has been the topic of numerous pharmaceutical studies with members being used for their medicinal properties such as anti-inflammatory (Abdellatif et al, 2018), antidiabetic (Pillai et al, 2019), antiviral (El-Sabbagh et al, 2009), analgesic (Karrouchi et al, 2016), antitumoral (Guillé n et al, 2017), catecholase (Karrouchi et al, 2018), and even as insecticides (Shi et al, 2017). In particular, pyrazolylacetamide derivatives are widely studied with increasing interest because of their antioxidant (Chkirate et al, 2019), antagonist (Chambers et al, 2010;Beswick et al, 2010) and anti-inflammatory (Sunder et al, 2013), as well as their antimicrobial potential and anticancer (Dev et al, 2017) activities.…”