Synthesis and Pharmacological Evaluation of Some Pyrazole Derivatives for Anti-Inflammatory and Analgesic Activity

Abstract

3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one obtained from phenyl hydrazine and ethyl acetoacetate was acetylated and then subjected to Claisen-Schmidt condensation with 4-hydroxy benzaldehyde to get a chalcone. This chalcone was cyclized with the help of hydroxylamine hydrochloride to form an isoxazole derivatives which were further condensed with various substituted aromatic aldehydes to obtain titled compounds (4aD1-4aD15). The structures of new synthesized compounds were confirmed by IR, 1H NMR and Mass spectral data. Synthesized derivatives were evaluated for their anti-inflammatory and analgesic activity. The compound 4aD3, 4aD8, 4aD9, 4aD10 and 4aD14 was found to have comparable anti-inflammatory activity with that of standard drug indomethacin. The compound 4aD3,4aD8, 4aD9, 4aD10 and 4aD11 was found to have comparable analgesic activity with that of standard drug tramadol. QSPR and Molecular Docking studies of the synthesized compounds were carried out to compare the physical property with biological activity. The compounds which have good pharmacological activity have good QSPR values which are in accordance with the observed anti-inflammatory activity. Docking studies were carried in COX I and COXII receptors. Most of the hydrogen bonds formed in docking studies are with the help of hetero atoms present in the parent nuclei pyrazole and isoxazole. This indicates the involvement of pyrazole and isoxazole nucleus in docking with COX 2 receptor and anti-inflammatory activity.