From indomethacin to a selective COX-2 inhibitor: Development of indolalkanoic acids as potent and selective cyclooxygenase-2 inhibitors

Black, W. Cameron; Bayly, Christopher I.; Belley, Michel; Chen, Chan; Charleson, S.; Denis, Danielle; Gauthier, J. Y.; Gordon, Robert J.; Guay, Daniel; Kargman, Stacia; Lau, Cheuk K.; Leblanc, Yves; Mancini, Joseph A.; Ouellet, Marc; Percival, David; Roy, Patrick; Skorey, Kathryn; Tagari, Philip; Vickers, Philip J.; Wong, Elizabeth; Xu, Li; Prasit, Petpiboon

doi:10.1016/0960-894x(96)00100-x

Cited by 102 publications

(44 citation statements)

References 15 publications

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“…Some experiments have reported structures in which the sulfonyl moiety on the aromatic ring is missing (3) [25][26][27] . Niedballa et al showed that sulfonyl moiety can be replaced with alkoxy groups 28 .…”

Section: Fragment-based Designmentioning

confidence: 99%

Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities

Khoshneviszadeh

Shahraki

Khoshneviszadeh

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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A set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2) inhibitors. These compounds were synthesized and screened for inhibition of cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inFammation. The results showed that 3-(2-(benzo-bis(4-methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2 inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant activity. The compound G3 with IC 50 value of 124 mM was the most potent compound in LOX inhibitory assay. Molecular docking was performed and a good agreement was observed between computational and experimental results.

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Section: Fragment-based Designmentioning

confidence: 99%

Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities

Khoshneviszadeh

Shahraki

Khoshneviszadeh

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…(1) replacement ofthe 4-chlorobenzoyl group with a 2,4,6-trichlorobenzoyl-or a 4-bromobenzyl group (examples 3 and 4) [107,108], (2) increasing the chain length of the 3-alkanoic acid group (example 5) [108], (3) neutralization ofthe carboxylic acid group via conversion to the corresponding esters (compd. 6) or amides (compd.…”

Section: Aryl Acetic Acids Indomethacinmentioning

confidence: 99%

Structural diversity of selective COX-2 inhibitors

Marnett

Kalgutkar

2004

COX-2 Inhibitors

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“…For example, the con- version of a free COOH group in indomethacin to Me ester gave a compound which was 132 times more selective as a COX-2 inhibitor than as a COX-1 inhibitor, IC 50 (COX-2) is 0.25 ¹M; IC 50 (COX-1) is ¹ 33 ¹M. By replacing the benzoyl group of indomethacin with 4-bromobenzyl and by extending the acetic acid side chain a series of potent and highly selective COX-2 inhibitors have been synthesized by Black et al [28]. Out of a number of compounds synthesized, compound 3 has the best in vitro and in vivo pro¯les.…”

Section: Chemical Manipulationsmentioning

confidence: 99%

Heterocyclic inflammation inhibitors

et al. 2004

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Non steroidal anti-in®ammatory drugs are the most widely used medicines for relief of pain. These drugs have some side e¬ects, particularly toxicity in the gastrointestinal tract and kidneys. Various approaches have been used for obtaining safer anti-in®ammatory drugs. In this review we have summarized the recent developments in the following areas; (i) Mode of action of NSAIDs, (ii) Role of COX-1 & COX-2 in in®ammation, (iii) Di¬erent approaches used to improve gastric tolerance i.e chemical manipulation, formulation & co-administration, development of non speci c (COX

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From indomethacin to a selective COX-2 inhibitor: Development of indolalkanoic acids as potent and selective cyclooxygenase-2 inhibitors

Cited by 102 publications

References 15 publications

Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities

Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities

Structural diversity of selective COX-2 inhibitors

Heterocyclic inflammation inhibitors

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