Synthesis of some novel bioactive 4-oxy/thio substituted-1H-pyrazol-5(4H)-ones via efficient cross-Claisen condensation

Ragavan, R. Venkat; Vijayakumar, V.; Kumari, N. Suchetha

doi:10.1016/j.ejmech.2009.04.010

Cited by 80 publications

(14 citation statements)

References 25 publications

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

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“…This 2 reacts with substituted amines forms RA1-RA9. The 1 H-NMR spectra of 3-methyl-1H-pyrazol-5(4H)-one (1) showed broad peak of -NH at δ 10.5 ppm two protons and presence of broad peak at δ 9.086 ppm due to one proton established that Nsubstitution occurs in product (2). The 1 H-NMR, MS, IR and elemental analysis supported the structure of title compounds.…”

Section: Chemistrymentioning

confidence: 63%

“…presence of K 2 CO 3 forms 1-(2-bromoethyl)-3-methyl-1H-pyrazol-5(4H)-one (2). Compound 2 further reacted with substituted amines gives formation of compound RA1-RA9.…”

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confidence: 99%

Synthesis, Antitumor and Antimicrobial Activities of Some Novel 1-(Substituted)-3-Methyl-1H-Pyrazol-5(4H)-One

Antre¹,

Cendilkumar²,

Nagarajan³

et al. 2011

J. Sci. Res.

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Several 1-(substituted)-3-methyl-1H-pyrazol-5(4H)-one as RA1-RA9 were synthesized and compounds were screened for antitumor activity against Ehrlich ascites carcinoma (EAC) cells and antimicrobial activity. Elemental analysis, mass spectral data, 1H-NMR, and IR confirmed the structure of the newly synthesized compounds. Some of the tested compounds showed good antitumor and antimicrobial activity. Compounds RA1, RA4, and RA9 exhibit highest antitumor activity against EAC cells in comparison with 5-flurouracil as standard drug.Keywords: Ehrlich ascites carcinoma; Pyrazolone; Antitumor; N-substitution; Antimicrobial.© 2012 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v4i1.7027 J. Sci. Res. 4 (1), 183-192 (2012)

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“…In continuation of our interest towards the synthesis of β-keto esters and pyrazolones [65-67], we made an attempt to synthesize β-keto esters from ethyl chloroformate in the presence of base which in turn are converted into pyrazolones in situ by the addition of either hydrazine or its derivatives, since we hypothesized that an enolate may react cleanly with highly electrophilic ethyl chloroformate to give β-keto esters. We tested our hypothesis in the synthesis of representative compound 12 by varying the solvents as well as bases (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

et al. 2013

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BackgroundPyrazolones are traditionally synthesized by the reaction of β-keto esters with hydrazine and its derivatives. There are methods to synthesize β-keto esters from esters and aldehydes, but these methods have main limitation in varying the substituents. Often, there are a number of methods such as acylation of enolates in which a chelating effect has been employed to lock the enolate anion using lithium and magnesium salts; however, these methods suffer from inconsistent yields in the case of aliphatic acylation. There are methods to synthesize β-keto esters from ketones like caboxylation of ketone enolates using carbon dioxide and carbon monoxide sources in the presence of palladium or transition metal catalysts. Currently, the most general and simple method to synthesize β-keto ester is the reaction of dimethyl or ethyl carbonate with ketone in the presence of strong bases which also requires long reaction time, use of excessive amount of reagent and inconsistent yield. These factors lead us to develop a simple method to synthesize β-keto esters by changing the base and reagent.ResultsA series of β-keto esters were synthesized from ketones and ethyl chloroformate in the presence of base which in turn are converted to pyrazolones and then subjected to cytotoxicity studies towards various cancer cell lines and antimicrobial activity studies towards various bacterial and fungal strains.ConclusionThe β-keto esters from ethyl chloroformate was successfully attempted, and the developed method is simple, fast and applicable to the ketones having the alkyl halogens, protecting groups like Boc and Cbz that were tolerated and proved to be useful in the synthesis of fused bicyclic and tricyclic pyrazolones efficiently using cyclic ketones. Since this method is successful for different ketones, it can be useful for the synthesis of pharmaceutically important pyrazolones also. The synthesized pyrazolones were subjected to antimicrobial, docking and cytotoxicity assay against ACHN (human renal cell carcinoma), Panc-1 (human pancreatic adenocarcinoma) and HCT-116 (human colon cancer) cell line, and lead molecules have been identified. Some of the compounds are found to have promising activity against different bacterial and fungal strains tested.

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Synthesis of some novel bioactive 4-oxy/thio substituted-1H-pyrazol-5(4H)-ones via efficient cross-Claisen condensation

Cited by 80 publications

References 25 publications

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

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

Synthesis, Antitumor and Antimicrobial Activities of Some Novel 1-(Substituted)-3-Methyl-1<i>H</i>-Pyrazol-5(4<i>H</i>)-One

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

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