Design, synthesis, in silico study and preliminary pharmacological evaluation of ibuprofen derivatives containing 1, 3, 4-Oxadiazole moiety

Four different ibuprofen derivatives were synthesized by modification of the carboxyl group to its bioisoster 1, 3, 4-oxadiazole heterocyclic ring, in which 2-position was substituted with different aromatic moieties. These derivatives aimed to increase the selectivity towered COX-2 rather than COX-1 by increase the bulkiness, and reduce the GIT ulceration and bleeding caused by the carboxyl group in ibuprofen. Acute anti-inflammatory study of the designed targeted compounds (IVa-IVd) was evaluated in vivo using egg-white induced edema model of inflammation in rat paw, with a dose equivalent to (100 mg/kg) of ibuprofen. A significant reduction of paw edema with respect to the effect of propylene glycol 50% v/v (control group) was obtained with all tested compounds. Compounds IVa, and IVd showed superior anti-inflammatory activity compared to standard (ibuprofen). All synthesized compounds were characterized, and identified using different physico-chemical parameters as melting points, and Retention factor (R-f) values, and confirmed using FT-IR spectrum, 1H NMR spectrum, and elemental microanalysis. The results of this search give evidence about the valid synthesis of 1, 3, 4-Oxadiazole derivatives of ibuprofen. Copyright (C) 2022 Elsevier Ltd. All rights reserved. Selection and peer-review under responsibility of the scientific committee of the XII th Biennial National Conference of Physics Academy of North East (PANE 2021).