Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents

Abstract

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles ( 4a-d) , 1,3,4-thiadiazoles ( 6a - d) , and pyrimidines ( 8a - d) , was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53–69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents

“…Moreover, there are some antipyrine-based commercially available drugs such as Famprofazone and Edaravone ( Sahoo et al, 2020 , Ebosie et al, 2021 , Mustafa et al, 2022 , Shaikh et al, 2023 ). In 2023, Al-Sanea and co-workers prepared an oxadiazolyl linked to antipyrine derivative I , which demonstrated anti-inflammatory activity and selective inhibitory activity against COX-2 enzymes ( Al-Sanea et al, 2023 ). Also, in 2022, Abu-Melha synthesized an antipyrine-thiazole hybrid II , which revealed respectable antibacterial activity ( Abu-Melha, 2022 ).…”

Novel quinazolines bearing 1,3,4-thiadiazole-aryl urea derivative as anticancer agents: design, synthesis, molecular docking, DFT and bioactivity evaluations

“…The solid that formed was filtered and washed with diethyl ether (Et 2 O), resulting in pure white solids known as adducts 8a-l. These adducts were then used in the subsequent step without requiring any additional purification steps [ 66 ].…”

New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study

“…By studying the inhibition affinity of gefitinib with the EGFR binding site, it was found that the quinazoline moiety fits into the ATP binding pocket in the kinase domain forming H-bond with hinge region due to N-1 and N-3 atoms. In addition, large aniline substituent and 6-morpholinylpropoxy group filled the hydrophobic pocket and the solvent region; respectively 49 , 50 . The molecular docking study showed that compound 5a and 10b showed the best binding affinity while compound 10a showed the lowest in comparison to the standard inhibitor gefitinib as shown in Table 7 , which agrees with the experimental data.…”