Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti‐Inflammatory Agents

Abstract

Two series of new 1-(alkyl/aryl)-3-{2-[(5-oxo-4,5-dihydro-1H-pyrazol-3-yl)amino]phenyl}thioureas 2a-h and 5-[2-(substituted amino)-1H-benzimidazol-1-yl]-4H-pyrazol-3-ols 3a-i were designed and synthesized as anti-inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non-selective inhibition of COX-1 and COX-2 enzymes which was consistent with their docking results. Compounds 2c, 2f, 2g, 3b, and 3g that showed the highest COX-2 inhibitory activity were selected for further in vivo testing as anti-inflammatory agents using diclofenac as a reference drug. Two of the test compounds (2c and 3b) showed potent anti-inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti-inflammatory agents was also provided.

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

“…Moreover, thiourea derivatives imparted strengthen activity compared with those with urea and guanidine. Ashraf et al [97] successfully prepared two series of pyrazolone analogues and tested their anti-inflammatory effect in vivo and in vitro. The derivative 132 and the enolate133 (Fig.…”

Tiyazol-fenilasetik asit bileşiklerinin dual antibakteriyel-COX enzim inhibitörleri olarak sentezleri

“…On the other, hand, promising COX inhibition potencies of compounds 2b and 2d displayed the positive contribution of chloro substituent to pharmacological activity. Thus, incorporation of this substituent in the chemical structures of new compounds may cause beneficial contribution to COX inhibition 13,14 .…”

“…As a new insight combine drugs such as COX inhibitory-antibacterial agent has attracted attention for treatment of such patients [12][13][14][15][16] .…”

Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18 Nanostructures for the Development of Antifungal Strategies

“…Thiourea derivatives are a class of privileged compounds, exhibiting a wide range of biological activities, such as antibacterial [ 9 ], antifungal [ 10 ], antituberculosis [ 11 ], antiviral [ 12 ], anticancer [ 13 ], anti-parasitic [ 14 ], anticonvulsant [ 15 ], anti-oxidant [ 16 ], analgesic [ 17 ] and anti-inflammatory [ 18 ]. Thiourea derivatives also display good coordination ability, being used as intermediates for a great variety of heterocyclic products, such as thiohydantoin [ 19 ], iminothiazolidinone [ 20 ], thioxopyrimidindione, 1,2,4-thiadiazoles [ 19 ], 2 H -1,2,4-thiadiazolo[2,3- a ]pyrimidine [ 21 ] etc.…”