INTRODUCTION Tissues in response to traumatic infections, post-ischaemia, toxicity and autoimmune injury cause inflammation and pain. The pathophysiological conditions such as evolution of persistent tissue damage of leucocytes, lymphocytes and collagen, the defensive process normally lead to recovery from noxious stimulus 1 . According to ORIENTAL JOURNAL OF CHEMISTRY www.orientjchem.org An International Open Free Access, Peer Reviewed Research Journal ISSN: 0970-020 X CODEN: OJCHEG 2015, Vol. 31, No. (4): Pg. 1873-1885 Synthesis and Anti-inflammatory Activity of Some New Thiadiazole Linked Pyrazole Benzene Sulphonamides as Cyclooxygenase Inhibitors MD. JAHANGIR ALAM, OZAIR ALAM*, MD. RAHMAT ALI, MOHD. JAVED NAIM and SUROOR AHMAD KHAN Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi-110062, India. *Corresponding author E-mail: dr.ozairalam@gmail.com http://dx.doi.org/10.13005/ojc/310404 (Received: October 04, 2015; Accepted: November 13, 2015) ABSTRACT A new series of thiadiazole linked pyrazole benzenesulfonamide derivatives were synthesized by the condensation of aldehydic pyrazole with aryl substituted thiadiazole amine followed by Schiff base reaction. The synthesized compounds (6a-o) were characterized by IR, NMR, and Mass spectral data, further evaluated their in-vivo anti-inflammatory, analgesic and in- vitro COX-II inhibition assay. The compounds 6b and 6m showed most significant in-vivo anti- inflammatory with 72.33 &71.17% inhibition along analgesic activity having 67.89% and 71.37 % respectively. Their selectivity against COX-II enzyme with selectivity index 67.81 and 66.38 was established for 6b and 6m, which is compared with Celecoxib. During the gastric ulceration study, selected compounds couldn’t observed any ulcerogenic effect on gastric mucosa.The in-silico pharmacokinetic profile and molecular docking study exposed very good binding affinity towards the Cyclooxygenase (COX-II) enzyme (PDB Id: 3PGH), therefore the compounds 6b and 6m are used as promising lead candidates for the support of drug development. Key words: Benzenesulfonamide, Cyclooxygenase, Prostanoids, Traumatic infections. WHO report approximately 90% of the illness are associated with inflammation and pain 2 . The inflammatory mediators of eicosanoids are activated by the nociceptors which leads to hyperalgesia 3 . The key focus of medicine is to reduce the pain and classical inflammation such as fever, redness and swelling, which are mediated by pro-inflammatory eicosanoids 4 . During eicosanoids pathway the cellular enzymatic activity of arachidonic acid