ABSTRACT
Forced degradation study of argatroban under conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH Q1A (R2), was accomplished. The drug showed sig-nificant degradation under hydrolysis (acidic, alkaline) and oxidation (peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products (DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by 1H NMR, 13C NMR, 2D NMR, Q-TOF-MSn and IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.
ABSTRACT
The primary effect of the NSAIDs is to inhibit cyclooxygenase (COX or prostaglandin synthase), thereby impairing the ultimate transformation of arachidonic acid to prostaglandins, prostacyclin, and thromboxanes. Two related isoforms of the COX enzyme have been described, COX-1 and COX-2. Identification of this cyclooxygenase-2 (COX-2) isoform resulted in the development of selective COX-2 inhibitors, with the hope of producing a safer analgesic and anti-inflammatory agent. The principal benefit with the selective COX-2 inhibitors is the production of comparable analgesia and antiinflammatory effects to the nonselective NSAIDs, but with fewer symptomatic gastric and duodenal ulcers and a decrease in gastrointestinal symptoms. In the present work, twelve novel series of xanthone derivatives (A1-A6 and B1-B6) were allowed to dock against PGHS-2(prostaglandin endoperoxide synthase-2) protein (PDB ID: 3LN1) to evaluate their comparative efficacy in terms of docking performance. The results are discussed on the basis of binding energy value.