Design and synthesis of new 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety as selective COX-2 inhibitors

Bekheit, Mohamed S.; Mohamed, Hanan A.; Abdel‐Wahab, Bakr F.; Fouad, Marwa A.

doi:10.1007/s00044-021-02716-7

Cited by 22 publications

(16 citation statements)

References 46 publications

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“…Despite the presence of several NSAIDs, the development of new NSAIDs is attractive, owing to the diverse inflammatory conditions and the need for optimized application in relation to disease and patient conditions. The recent development of NSAIDs comprises modified methyl sulphonyl [ 17 ]; pyrimidine-5-carbonitrile hybrids [ 18 ], pyrazole derivatives [ 19 ], indanone containing spiroisoxazoline derivatives [ 20 ], triazole, and oxadiazole compounds [ 21 , 22 ]. Despite the growing repository of newly synthesized NSAIDs, the development of new compounds is strictly required due to the side effects of the currently approved NSAIDs.…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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The goal of achieving anti-inflammatory efficacy with the fewest possible adverse effects through selective COX-2 inhibition is still being investigated in order to develop drugs with safe profiles. This work shows the efficacy and safety profile of two novel benzimidazole piperidine and phenoxy pyridine derivatives in reaching this goal, which would be considered a major achievement in inflammatory therapy. The compounds were evaluated by virtual screening campaign, in vitro cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibition, in vivo carrageenan-induced rat paw edema assay, cytotoxicity against Raw264.7 cells, and histopathological examination of rat paw and stomach. Two new compounds, compound 1 ([(2-{[3-(4-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]carbonyl}phenyl)amino]acetic acid) and compound 2 (ethyl 1-(5-cyano-2-hydroxyphenyl)-4-oxo-5-phenoxy-1,4-dihydropyridine-3-carboxylate) showed high selectivity against COX-2, favourable drug-likeness and ADME descriptors, a lack of cytotoxicity, relived paw edema, and inflammation without noticeable side effects on the stomach. These two compounds are promising new NSAIDs.

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Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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“…Several 1,4,5-trisubstituted 1,2,3-triazole-4-carboxamides showed high affinity in the nanomolar concentration range toward Hsp90 associated with cell proliferation inhibition (Taddei et al, 2014;Giannini et al, 2015). Moreover,-5methyl-1H-1,2,3-triazol-1-yl]benzenesulfonamide was found to act as a COX-2 inhibitor (Bekheit et al, 2021).…”

Section: Chemical Contextmentioning

confidence: 99%

Synthesis, crystal structure and Hirshfeld surface analysis of 5-cyclopropyl-N-(2-hydroxyethyl)-1-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxamide

Pokhodylo¹,

Slyvka²,

Pavlyuk³

2021

Acta Crystallogr E Cryst Commun

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The title compound, C15H18N4O2, was obtained via a two-step synthesis (Dimroth reaction and amidation) for anticancer activity screening and was selected from a 1H-1,2,3-triazole-4-carboxamide library. The cyclopropyl ring is oriented almost perpendicular to the benzene ring [dihedral angle = 87.9 (1)°], while the dihedral angle between the mean plane of the cyclopropyl ring and that of the triazole ring is 55.6 (1)°. In the crystal, the molecules are linked by O—H...O and C—H...N interactions into infinite ribbons propagating in the [001] direction, which are interconnected by weak C—H...O interactions into layers. The intermolecular interactions were characterized via Hirshfeld surface analysis, which indicated that the largest fingerprint contact percentages are H...H (55.5%), N...H/H...N (15.4%), C...H/H...C (13.2%) and O...H/H...O (12.9%).

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“…Recently, Al-Wahaibi et al 79 In another study, Bekheit et al 80 reported a 1,4,5trisubstituted triazole-based selective COX-2 inhibitor bearing a sulfonamide moiety (18) with IC 50 = 2.61-14.82 μM (SI = 1.95-6.98) (Fig. 17).…”

Section: Rsc Medicinal Chemistry Reviewmentioning

confidence: 99%