Synthesis and biological evaluation of N-substituted-3,5-diphenyl-2-pyrazoline derivatives as cyclooxygenase (COX-2) inhibitors

Fioravanti, Rossella; Bolasco, Adriana; Manna, Fedele; Rossi, Francesca; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano; Cirilli, Roberto

doi:10.1016/j.ejmech.2010.10.005

Cited by 112 publications

(55 citation statements)

References 21 publications

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“…Fioravanti et al 58 synthesized 18 analogous of 1-N-substituted-3,5-diphenyl-2-pyrazoline derivatives and evaluated the cyclooxygenase activity of these compounds. They synthesized compounds in which the N1 of pyrazoline was substituted with either acetyl moiety or thiocarbamoyl moiety.…”

Section: Cox-ii Inhibitory Activitymentioning

confidence: 99%

4,5-Dihydro-1H-pyrazole: an indispensable scaffold

Alex

Kumar

2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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Pyrazoles, categorized as nitrogen-containing heterocycles, are well known for their interminable participation in the field of perpetual research and development of therapeutical active agents. As a consequence pyrazoles became an inevitable core of numerous drugs having diverse activities. The broad spectrum of activities portrayed by the pyrazoles instigated the researchers to modify the pyrazole ring as 4,5-dihydro-1H-pyrazoles commonly known as 2-pyrazolines. The present review is a concerted effort to retrace compounds covered from 2009-till date which owe diverse biological activities to the 2-pyrazoline scaffold and also condenses the retro-synthetic approaches employed for their synthesis. This endeavor culminated in revelation that inhibitory potential varied when the substituents in particular N-substituents of 2-pyrazolines were altered.

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Section: Cox-ii Inhibitory Activitymentioning

confidence: 99%

4,5-Dihydro-1H-pyrazole: an indispensable scaffold

Alex

Kumar

2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Therefore, synthetic approaches based upon chemical modification of NSAIDs were taken with the aim of improving NSAID safety profile. [7][8][9][10] The core pyrazolone structure generally attracted widespread attention because of the diversity of biological activity as they showed anti-inflammatory [11][12][13] analgesic, 14,15) antitumor, 16) antimicrobial, 17,18) hypoglycemic, 19) and antitubercular 20) activities. One of the first synthetic organic compounds that used as an important drug and having a pyrazolone nucleus was antipyrine I.…”

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confidence: 99%

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

et al. 2013

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Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3-and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.Key words pyrazolone; acetic acid; quantitative structure-activity relationship; cyclooxygenase inhibition; anti-inflammatory Non steroidal anti-inflammatory drugs (NSAIDs) were known as important class of therapeutic agents for the alleviation of pain and inflammation. The pharmacological activity of NSAIDs is due to the inhibition of prostaglandins biosynthesis from arachidonic acid through inhibiting cyclooxygenases (COXs).1,2) However, long term use of NSAIDs was associated with several side effects such as gastrointestinal mucosal damage, bleeding, intolerance, and renal toxicity. 3-6)The gastrointestinal (GI) damage from NSAIDs generally attributes to two factors, i.e., local irritation by the carboxylic acid moiety, common to most NSAIDs (topical effect) and decreased tissue prostaglandins production which maintains GI health and homeostasis. Therefore, synthetic approaches based upon chemical modification of NSAIDs were taken with the aim of improving NSAID safety profile. 7-10)The core pyrazolone structure generally attracted widespread attention because of the diversity of biological activity as they showed anti-inflammatory [11][12][13] analgesic, 14,15) antitumor, 16) antimicrobial, 17,18) hypoglycemic, 19) and antitubercular 20) activities. One of the first synthetic organic compounds that used as an important drug and having a pyrazolone nucleus was antipyrine I. 21) In addition, many pyrazolones like aminophenazone II, propyphenazone III, and famorofazone IV (Fig. 1) are widely used as anti-inflammatory, analgesic, and antipyretic drugs. 7,22,23) Besides, different pyrazolones found to possess significant anti-inflammatory activity as compounds V, 24) VI, 11) VII, 11) and VIII 13) (Fig. 2). Thus, our main objective is to design novel pyrazolone derivatives to be further explored as powerful and novel nonulcerogenic anti-inflammatory lead candidates. Some of these derivatives contain acidic centers with further esterification aiming to decrease the local side effects that might be attained by its acidic moieties.The synthesized compounds were evaluated for their antiinflammatory and analgesic activities. Ulcerogenic liability was also performed; in addition, evaluation for the...

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“…The potential effects of the test drugs on total hCOX activity (bis-dioxygenase and peroxidase reactions) were investigated by measuring their effects on the oxidation of N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) to N,N,N′,N′-tetramethyl-p-phenylenedaimine, using AA as common substrate for both hCOX-1 and hCOX-2, microsomal COX-2 prepared from insect cells (Sf21 cells) infected with recombinant baculovirus containing cDNA inserts for hCOX-2 (Sigma Aldrich Química S.A., Alcobendas, Spain), and COX-1 from human platelet microsomes (obtained as described in the above paragraph since, unlike hCOX-2, hCOX-1 is not available commercially) [14]. …”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors

Vernieri

Gómez-Monterrey

Milite

et al. 2013

Journal of Amino Acids

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Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 203 possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.

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Synthesis and biological evaluation of N-substituted-3,5-diphenyl-2-pyrazoline derivatives as cyclooxygenase (COX-2) inhibitors

Cited by 112 publications

References 21 publications

4,5-Dihydro-1H-pyrazole: an indispensable scaffold

4,5-Dihydro-1H-pyrazole: an indispensable scaffold

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors

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