Synthesis, anti-inflammatory, cyclooxygenases inhibitions assays and histopathological study of poly-substituted 1,3,5-triazines: Confirmation of regiospecific pyrazole cyclization by HMBC

Three novel triazines series were prepared. These series are pyrazolines (4a and 4b), pyrazoles (6a, 6b and 8a-d) and isoxazoles (7a and 7b). Such series were designed as COX-2 inhibitors. All compounds were characterized by using spectroscopic methods and elemental analysis. Regarding COX-2, compounds 5b, 4a and 3b were the most active with IC50 in the range of 0.55-0.87 mu M. Most of synthesized compounds were relatively more potent to celecoxib (0.78 mu M), diclofenac (2.94 mu M) and indomethacin (7.24 mu M). A molecular modeling study was performed for the most active compounds. Histopathological evaluation also was done to estimate the safety of compounds. Finally, structure elucidation of pyrazole 8 was studied by 2D NMR. (C) 2016 Published by Elsevier Masson SAS.