Synthesis and Activity of a New Methoxytetrahydropyran Derivative as Dual Cyclooxygenase-2/5-Lipoxygenase Inhibitor

Barbey, S.; Goossens, Laurence; Taverne, Thierry; Cornet, Joséphine; Choesmel, Valérie; Rouaud, Céline; Gimeno, G.; Yannic-Arnoult, Sylvie; Michaux, Catherine; Charlier, Caroline; Houssin, Raymond; Henichart, J. P.

doi:10.1016/s0960-894x(02)00013-6

Cited by 64 publications

(33 citation statements)

References 21 publications

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“…In addition, hybrid NSAIDs that exhibit dual COX/5-LOX inhibition have been explored (117). In an elegant study Henichart and coworkers prepared hybrid dual COX/5-LOX inhibitors by combining COX-2 and 5-LOX pharmacophores (138). In this regard, compound 49 (140,141).…”

Section: Dual Cox and Lipoxygenase (Lox) Inhibitorsmentioning

confidence: 99%

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Rao

Knaus²

2008

J Pharm Pharm Sci

579

391

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ABSTRACT. Purpose. NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects. Methods. Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries. Results. A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. Conclusions. A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.

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Section: Dual Cox and Lipoxygenase (Lox) Inhibitorsmentioning

confidence: 99%

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Rao

Knaus²

2008

J Pharm Pharm Sci

579

391

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“…Barbey et al [69] synthesized methoxytetrahydropyran derivative as dual cyclooxygenase-2=5-lipoxygenase inhibitor and identified it as an anticancer agent. Pommery et al [70] synthesized structurally related diaminopyrazole derivatives 303a-s (Fig.…”

Section: Cox and Lox Inhibitorsmentioning

confidence: 99%

Anticancer Activity of Pyrazole via Different Biological Mechanisms

Chauhan

Paliwal

Chauhan

2014

Synthetic Communications

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In the past few years pyrazole derivatives have attracted increasing attention because of their numerous potential pharmacological applications. Changes in their structure have offered a high degree of diversity that has proven useful for the development of new medicinal agents with improved potency and less toxicity. This review focuses on the recent developments in pyrazole along with their structure-activity relationship (SAR), particularly for anticancer activity. The review covers SAR for active pyrazole molecules such as cyclin dependent kinase (CDK) inhibitor (modulator), aurora kinase inhibitors (modulator), break point cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitors (modulator), heat shock protein (HSP 90) inhibitors (modulator), polo-like kinase inhibitors (modulator), cyclo-oxygenase (COX) and lypo-oxygenase (LOX) inhibitors (modulator), epithelial growth factor receptor (EGFR) inhibitors (modulator), reticular activating system-neuro endocrine tumor (Ras-Net) ETS-like transcription factor (Elk-3) pathway inhibitors (modulator), and DNA binding agent.

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“…Typically, they have been applied as thiazide and loop diuretics [45]. The sulfonamide COX-1/ COX-2 and COX-2 inhibitors such as Celecoxib, SC-558, Rofecoxib, and DuP-697 have been prescribed against inflammation [46,47], pain [48,49], and cancers [50,51]. Another area of sulfonamide drugs includes HIV protease [52] and reverse transcriptase inhibitors [53].…”

Section: Equation and Descriptorsmentioning

confidence: 99%

Indole-like Trk receptor antagonists

Tammiku-Taul

Park

Jaanson

et al. 2016

European Journal of Medicinal Chemistry

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The virtual screening for new scaffolds for TrkA receptor antagonists resulted in potential low molecular weight drug candidates for the treatment of neuropathic pain and cancer. In particular, the compound (Z)-3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxindole and its derivatives were assessed for their inhibitory activity against Trk receptors. The IC50 values were computationally predicted in combination of molecular and fragment-based QSAR. Thereafter, based on the structure-activity relationships (SAR), a series of new compounds were designed and synthesized. Among the final selection of 13 compounds, (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-N-methyl-2-oxindole-5-sulfonamide showed the best TrkA inhibitory activity using both biochemical and cellular assays and (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-2-oxindole-5-sulfonamide was the most potent inhibitor of TrkB and TrkC.

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Synthesis and Activity of a New Methoxytetrahydropyran Derivative as Dual Cyclooxygenase-2/5-Lipoxygenase Inhibitor

Cited by 64 publications

References 21 publications

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Anticancer Activity of Pyrazole via Different Biological Mechanisms

Indole-like Trk receptor antagonists

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