Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

• Published in: Bioorganic chemistry Vol. 89; p. 103007
• Main Authors: Sharma, Vrinda, Bhatia, Parth, Alam, Ozair, Javed Naim, Mohd, Nawaz, Farah, Ahmad Sheikh, Aadil, Jha, Mukund
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019
• Subjects: COX-2; Indole; Oxazole; Pyrazole; SAR; Val; Ile; PGH2; Oxazole; A549; Gln; MTT; Glu; HWB; DFT; Trp; Gly; DENV; IC50; CCK-8; nM; IL; MIA; EAC; MS; PGG2; IP; AI; IR; CEM; LD50; TXA2; PASS; LOX; Arg; µM; Ser; COX-2; SAR; Indole; MCF-7; G1; Phe; Pyrazole; LPS; ADME-T; SD; PTGS; RAW264.7; NSAIDs; SI; HepG2; ED50; DMF; Asp; Thr; PGE2; ACE; PGI2; J774; HRBC; SPF/VAF; Tyr; COX; Hela; NMR; His; BAS; NIH/3T3; TNF-α; NAG; Ala; B16-F10; Leu; HaCaT; COPD
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103007

[Display omitted] •COX is a family of isozymes responsible for the catalysing reactions of Arachidonic acid.•COX-2 inhibitors based on Pyrazole, Indole, Oxazole, Pyridine and Pyrrole are studied using SAR and docking.•Novel COX-2 inhibitors have been developed with an improved safety profile and with a higher potency. Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.