SYNTHESIS AND BIOLOGICAL SIGNIFICANCE OF PYRAZOLONES: A REVIEW
HTML Full TextSYNTHESIS AND BIOLOGICAL SIGNIFICANCE OF PYRAZOLONES: A REVIEW
Poonam Gupta*, Jitendra K. Gupta and A. K. Halve
School of studies in Chemistry, Jiwaji University, Gwalior-474011, Madhya Pradesh, India
ABSTRACT: Heterocyclic compounds are acquiring more importance in recent years because of their pharmacological activities. Pyrazolones have a particular value due to their broad spectrum of biological activity and their wide ranging utility as synthetic tools in the design of various bioactive molecules. Pyrazolone is a five membered lactum ring, containing two nitrogen and one ketonic group in its structure. In addition, pyrazolones possess antimicrobial, antifungal, antimycobacterial, antibacterial, anti-inflammatory, antitumor, gastric secretion stimulatory, antidepressant and antifilarial activities. They also serve as precursors for dyes, pigments, pesticides and chelating agents, besides finding applications in the extraction and separation of various metal ions. The high therapeutic properties of the pyrazolone releted drugs have encouraged the medicinal chemists to synthesized a large number of novel chemotherapeutic agents. Numerous methods for the synthesis of pyrazolone and also their various structure reactions offer enormous scope in the field of medicinal chemistry. This articles aims to review the work reported, their chemistry and biological activities of pyrazolone during past years.
Keywords: |
Pyrazolone,
Heterocyclic, Antibacterial,
Antifungal and Antitumor
INTRODUCTION: Since last two decades a rapid progress in synthetic organic chemistry is associated with a search for new compounds with desired properties. Such compounds are widely used in pharmaceutical industries. Among these, the heterocycles form the largest of the classical division of organic chemistry and are of immense biological and industrial importance. The majority of biologically active compounds are heterocycles also applicative as additives and modifiers used in industries of cosmetics, photography, information storage and plastics. Heterocyclic compounds are also used in pharmacy and agriculture.
Analysis of scientific papers in the last two decades revealed that there is a general trend in research for new drugs involving modification of existing biologically active matrices and molecular design of the structures of compounds.
In the recent years much attention has been focused on the synthesis of heterocycles containing nitrogen atom because of their biological and medicinal importance including ontological research. They are widely distributed in nature and are essential for life. Pyrazolones is a five member heterocyclic compound containing one ketonic group and two nitrogen atoms adjacent to each other. In 1883, Knorr et al 1 gave the generic name pyrazole to above class of the compounds, which is a five member unsaturated ring compound with two adjacent nitrogen atoms. Antipyrine was the first pyrazolone derivative for clinical use and was synthesized in 1883 2. It was used as the first agent to reduce fever and also for arthritis. There are three possible heteropyrazolines [1, 2, 3] in which carbonyl group is adjacent to nitrogen.
(1) (2) (3)
The carbonyl at position five leads to 5-hydroxyl pyrazoles [4], since the 5-hydroxy compound exhibits pronounced enol character, tautomeric forms shown below for the 1-phenylderivative are the fundamental structures involved in the pyrazolone reactions.
1-PHENYL-5-PYRAZOLONE (4)
Pyrazolone derivatives are an important class of heterocyclic compounds that occur in many drugs and synthetic products 3, 4. These compounds exhibit remarkable analgesic 5, antitubercular 6, antifungal, antibacterial 7, anti-inflammatory 8, antioxidant and antitumor activities 9. Due to their easier preparation and rich biological activity, pyrazolone framework plays an essential role and represents an interesting template for combinatorial and medicinal chemistry.
Pyrazolones are pharmacophores of numerous compounds (Fig. 1) that display activities such as analgesic and antipyretic (propylphenazone, phenazone, metamizole etc.) 10, anti-cancer (TELIN) 11, anti-ischemic (edaravone) 12, and anti-anxiolytic 13. Pyrazolones are gaining importance especially in drug discovery programs towards cerebral ischaemia 14 and cardiovascular diseases 15, 16.
Due to its diverse pharmacological properties, the chemistry of pyrazolones is gaining attention, and there have been numerous novel methodologies reported recently 17. We describe here in our research findings in this area.
FIG. 1: BIOLOGICALLY IMPORTANT PYRAZOLONES
Synthesis of Pyrazolone Derivatives:
By refluxing methods:
Sujatha et al. 18 have been reported the preparation of 4,4’-(arylmethylene) bis (1H-pyrazol-5-ols) 3 has been accomplished by tandem Knoevenagel–Michael reaction of two equivalents of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one 1 with various aromatic aldehydes 2 catalyzed by ceric ammonium nitrate (CAN) in water.
SCHEME 1: SYNTHESIS OF 4,4’-(ARYLMETHYLENE)BIS(1H-PYRAZOL-5-OLS) USING CERIC AMMONIUM NITRATE (CAN) AS CATALYST
Liu et al.19 have been reported a novel solid-state reversible fluorescence photo switching system (FPS) based on photochromism of photochromic pyrazolones has been developed by employing phosphor Sr2P2O7 co-doped with europium ion and chlorine ion (Sr2P2O7–EC). (3-chlorophenyl)(5-hydroxy-1,3-diphenyl-1H-pyrazol-4-yl)methanone 4 react with N-phenyl hydrazinecarboxamide 5 to form 1,3-diphenyl-4-(3-chlorobenzal)-5-hydroxypyrazole-4-phenylsemi carbazone 6 as the fluorescence dye and the photochromic compound, respectively.
SCHEME 2: SYNTHESIS OF PHOTOCHROMIC PYRAZOLONES BASED ON PHOTOCHROMISM BY EMPLOYING PHOAPHOR Sr2P2O7
Baciu-Atudosie et al.20 have been reported a simple one-pot approach for the synthesis of new 5-substituted-2-[2-(2-substituted-10H-phenothiazin-10-yl)-2-oxoethyl]-2,4-dihydro-3H-pyrazol-3-one 10 containing a phenothiazine unit by reaction of N-chloroacetyl compound 7, ethyl acetoacetate 9 with hydrazine hydrate 8.
SCHEME 3: SYNTHESIS OF NEW PYRAZOLONES CONTAINING A PHENOTHIAZINE UNIT
Kumar et al.21 have been reported the synthesis of 1-(4-methylcoumarinyl-7-oxyacetyl)-3,5-dimethyl-4-(arylazo)pyrazoles 14 by reaction of 1,3-diketo-1,3-dimethyl-2-(arylazo)propane 12 and 4-methylcoumarinyl-7-oxyacetic acid hydrazide 11 in glacial acetic acid was refluxed for 10 h. And the synthesis of 1-(4-methylcoumarinyl-7-oxyacetyl)-3-methyl-4-(substituted phenyl) hydrazono-2-pyrazolin-5-one Ethyl-2-(substituted phenyl) hydrazono-3-oxobutyrate 15 was dissolved in glacial acetic acid and 4-methylcoumarinyl-7-oxyacetic acid hydrazide 13 was refluxed for 4 h.
SCHEME 4: SYNTHESIS OF 1-(4-METHYLCOUMARINYL-7-OXYACETYL)-3, 5-DIMETHYL-4-(ARYLAZO) PYRAZOLES AND 1-(4-METHYLCOUMARINYL-7-OXYACETYL)-3-METHYL-4-(SUBSTITUTED PHENYL) HYDRAZONO-2-PYRAZOLIN-5-ONE ETHYL-2-(SUBSTITUTED PHENYL) HYDRAZONO-3-OXOBUTYRATE
Gunasekaran et al.22 have been reported a series of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones 20 has been synthesized by one-pot, four-component sequential reactions of phenyl hydrazine 16, methyl acetoacetate 17, β-naphthol 18 and aromatic aldehydes 19 in the presence of p-toluenesulphonic acid in water in good yields.
SCHEME 5: SYNTHESIS OF 2-ARYL-5-METHYL-2, 3-DIHYDRO-1H-3-PYRAZOLONES IN PRESENCE OF p-TSA
Shah et al.23 have been reported Mannich reaction of various ethyl-2-substituted phenyl hydrazono-3-oxobutyrates 22 with furan-2-carbohydrazide 23 afforded 1-(furan-2-carbonyl)-3-methyl-4-(2-phenyl hydrazono)-1H-pyrazol-5(4H)-one 24.
SCHEME 6: SYNTHESIS OF 1-(FURAN-2-CARBONYL)-3-METHYL-4-(2-PHENYL HYDRAZONO)-1H-PYRAZOL-5(4H)-ONE BY MANNICH REACTION.
Mosaddegh et al. 24 heve been reported the synthesis of 4,4’-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) 27 was performed effectively by the reaction of aryl aldehydes 26 and 1-phenyl-3-methyl-5-pyrazolone 25 in the presence of a catalytic amount of Ce(SO4)2.4H2O as reusable and environmentally friendly catalyst in water/ethanol solution. The method has the advantages of high yields, short reaction time, simple work-up and reusability of catalyst.
SCHEME 7: SYNTHESIS OF 4,4’-(ARYLMETHYLENE)BIS(3-METHYL-1-PHENYL-1H-PYRAZOL-5-OL) BY USING Ce(SO4)2.4H2O
Ahmad et al. 25 have been reported two novel series of 1-long chain alkanoyl/ alkenoyl/ hydroxyalkenoyl-3-methyl-1H-pyrazol-5(4H)-ones 30 and 2-long chain alkenoyl/hydroxyalkenoyl-3H-phthalazin-1,4-diones 32 it is achieved by the reaction of ethylacetoacetate 29 /phthalic anhydride 31 and hydrazides. Compounds 30 were synthesized by the cyclization reaction between ethylacetoacetate and hydrazides. Compounds 32 were synthesized by the reaction of phthalic anhydride and hydrazides in absolute ethanol/glacial AcOH.
SCHEME 8: SYNTHESIS OF HYDROXYALKENOYL-3-METHYL-1H-PYRAZOL-5(4H)-ONES
Ragavan et al. 26 have been reported Oxy/thio substituted-β-keto esters were synthesized through an efficient cross-Claisen condensation of aryl oxy/thio acetic acid ethyl esters 33 with acid chlorides 34, they form a intermediate 35 then it is converted into 4-oxy/thio substituted-1H-pyrazol-5(4H)-ones 36 by the addition of hydrazine or hydrazine derivatives.
SCHEME 9: SYNTHESIS OF 4-OXY/THIO SUBSTITUTED PYRAZOLONES VIA CROSS-CLAISEN CONDENSATION
Konkov et al.27 have been reported various pyrazole and dihydropyrazolones containing an adamantane fragment were synthesized from adamantyl-substituted 1,3- and 1,4-diketones, ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates (R=CN, Ac), and ethyl 2-(1-adamantylcarbonyl)-4-oxo-4-phenylbutanoate. Compound 37 reacted with hydrazine and phenylhydrazine to give 4-[2-(1-adamantyl)-2-oxoethyl]-3-methyl-4,5-dihydro-1H-pyrazol-5-ones 38.
SCHEME10: SYNTHESIS OF DIHYDROPYRAZOLONES CONTAINING AN ADAMANTANE FRAGMENT
Bran et al. 28 have been reported a series of bisindolylpyrazolone 40, 41 derivatives by the reaction of substituted β-ketoester 39, comphoric acid and ethylaminoethylhydrazine in ethanol medium.
SCHEME11: SYNTHESIS OF BISINDOLYLPYRAZOLONE DERIVATIVES
Burja et al. 29 have been reported a series of pyrazolone-fused combretastatins 49 and their precursors were synthesized by multicomponant reaction method which were completed in multisteps. At the last step methanolic solution of NaOH was added to a stirred mixture of 48 in CH2Cl2/MeOH at room temperature.
SCHEME12: SYNTHESIS OF THE FIRST PYRAZOLONE-FUSED COMBRETASTSTIN DERIVATIVES AND ITS PRECURSORS
Shamsuzzaman et al. 30 have been reported a convenient synthesis of a new series of nano steroidal pyrazolones 51, Cyanoacetohydrazide was added in an equimolar ratio to a solution of steroidal ketones 50 in acetic acid. The reaction mixture was stirred under refluxing for 7 h.
SCHEME13: SYNTHESIS OF NANO STEROIDAL PYRAZOLONES
Laufersweiler et al. 31 have been reported novel substituted [5,5]-bicyclic pyrazolones 56 were prepared in multisteps. Reaction start with t-Boc and benzyl carbazate 52 to gave keton. Ketone 53 react with borane dimethylsulfide and gave a intermediate 54, after that hydrogenolysis followed by acylation with 2-methylsulfanyl- pyrimidine-4-carbonyl chloride gave bis-acylated pyrazolidine 55. Ring closure proceeded an intramolecular cyclocondensation to form the pyrazolone. This was followed by oxidation of the methyl sulfide and subsequent displacement with an appropriate nucleophile to give the final compounds 56.
SCHEME14: SYNTHESIS OF NOVEL SUBSTITUTED [5,5]-BICYCLIC PYRZAZOLONES
Tripathy et al. 32 have been reported the synthesis of the unsubstituted pyrazolone 61, accomplished by the reaction of β-ketoester 57 react with semicarbazone which were followed by rearrangement to 1,2,3-thiadiazole in presence of thionyl chloride to gave 1,2,3-thiadiazole 5-carboxylic acid ethyl ester 60. Subsequent β-ketoester formation followed by cyclization with hydrazine resulted in the pyrazolone 61. Similar condensation with indole carboxaldehydes resulted in product 62.
SCHEME15: SYNTHESIS OF UNSUBSTITUTED PYRAZOLONE DERIVATIVES
Huang et al.33 have been reported an efficient and convenient method for the bromination of pyrazolones 65 and 5-hydroxypyrazoles 66 were developed 1,3-ketoester 63 and hydrazines 64 were added glacial acetic acid by using N-bromobenzamide 67 in THF at room temperature. This new method provided di-bromimated pyrazolones in excellent yields.
SCHEME16: SYNTHESIS OF DI-BROMIMATED PYRAZOLONES DERIVATIVES BY USING N-BROMOBENZAMIDE IN THF
Kadam et al. 34 have been repoted a novel synthesis of 3-amino-4-(4I-substituted benzylidene) - 1H-pyrazol-5(4H)-one derivatives 72 and 3-amino-4-(4I-substitued benzylidene) - 4, 5 - dihydro-5-oxopyrazole-1-carbothioamide derivatives 73 by the reaction of substituted benzaldehyde/ heteroaldehyde 70, ethylcyano acetate 71 and thiosemicarbazide was heated in presence of PEG-400.
SCHEME 17: SYNTHESIS OF TWO TYPE OF PYRAZOLONE DERIVATIVES
Mehta et al. 35have been reported the synthesis of diphenylic bispyrazole 76, 77 and diphenylic bispyrazolone compounds 79, 80. According to the method reported in the literature36, these derivatives have been synthesized by the reaction of 4,4'-sustituted dianiline 74 react with acetylacetone and ethylacetoacetate.
Compound 75 and 78 were reacted with hydrazine hydrate or phenyl hydrazine in CH3COOH. The reaction mixture was then allowed to reflux for 2 h or 6 h respectively with continuous stirring. After refluxing, it was allowed to cool at room temperature. The yellowish product obtained, was filtered and recrystallized using acetone.
Reagents: (i) NaNO2, H2SO4, 0-5oC (iia) Coupling-acetylacetone, 0-5oC (iib) Coupling-methyl acetoacetate, 0-5oC (iiia) Cyclization-hydrazine hydrate, EtOH, MW or ∆ (iiib) Cyclization-phenyl hydrazine, AcOH, MW or ∆ (iiic) Cyclization-hydrazine hydrate, EtOH, MW or ∆ (iiid) Cyclization-phenyl hydrazine, AcOH, MW or ∆
SCHEME18: SYNTHESIS OF DIPHENYLIC BISPYRAZOLE OR BISPYRAZOLONE COMPOUNDS
Ghosh et al. 37 have been reported a glacial acetic acid catalyzed reaction for the combinatorial synthesis of highly functionalized benzylpyrazolyl coumarin 85 prepared by a green one-pot four-component reaction between aryl hydrazine/ hydrazine hydrate 81, ethyl acetoacetate 82, aromatic aldehydes 83 and 4-hydroxycoumarin 84 in water medium under refluxing conditions.
SCHEME 19: GREEN SYNTHESIS OF BENZYLPYRAZOLYL COUMARINS
By microwave irridation:
Tu et al. 38 have been synthesized C-tethered bispyrazol-5-ols 89 via multicomponent domino reactions of acetylenedicarboxylates 86, phenylhydrazine 87 and aromatic aldehydes 88 under microwave irradiation.
SCHEME 1: SYNTHESIS OF C-TETHERED BISPYRAZOL-5-OLS
Sivakumar et al. 39 have been reported an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl) carbonyl]-2,4-dihydro-3H-pyrazol-3-one 95 have been described by using multicomponant with microwave techniques. Microwave assisted reactions showed that require shorter reaction time and good yield.
SCHEME 2: SYNTHESIS OF 5-METHYL-2-[(2-OXO-2H-CHROMEN-3-YL)CARBONYL]-2,4-DIHYDRO-3H-PYRAZOL-3-ONE
Antre et al. 40 have been reported various 4-(2-amino-6-(substituted)pyrimidin-4-yl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one derivatives 101 and their Schiff bases 102 were synthesized by the reaction of hydrazide 96 and ethylacetoacetate 97 to form pyrazolone derivatives 98. Compound 98 further react with acetyl chloride and prepared compound 99, therefore it has react with aromatic aldehyde and guanidine hydrochloride to gave pyrazolone derivatives 100 and 101. Afterthat pyrazolone derivatives 101 again react with aromatic aldehyde and formed pyrazolone Schiff base derivatives 102.
SCHEME 3: SYNTHESIS OF PYRAZOLONE DERIVATIVES AND THEIR SCHIFF BASES
Zang et al. 41 have been reported the synthesis of 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-phenyl-methyl] – 5 – methyl – 2 - phen-yl-1,2-dihydro-pyrazol-3-ones 106 through the condensation reaction of arylaldehydes 103 and 3-methyl-1-phenyl-5-pyrazolone 104 with Ionic liquid [HMIM]HSO4 catalyst 105 under ultrasonic irradiation at room temperature. The present methodology offers several advantages such as excellent yields, simple procedure and mild conditions.
SCHEME 4: SYNTHESIS OF 4-[(5-HYDROXY-3-METHYL-1-PHENYL-1H-PYRAZOL-4-YL)-PHENYL-METHYL]-5-METHYL-2-PHEN-YL-1,2-DIHYDRO-PYRAZOL-3-ONES USING [HMIM]HSO4 CATALYST
Ziarati et al. 42 have been reported simple and green process to prepare copper iodide in nano scale via sonication was carried out. Subsequently, this nanoparticles was used as an efficient catalyst for the synthesis of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones 111 via four-component reaction of hydrazine 107, ethyl acetoacetate 108, aldehyde 109 and β-naphthol 110 in water under ultrasound irradiation.
SCHEME 5: SYNTHESIS OF 2-ARYL-5-METHYL-2,3-DIHYDRO-1H-3-PYRAZOLONES USING CuI NANOPARTICLES
Gadhave et al. 43 have been reported a series of novel fluorine containing pyrazole-pyrazolone 118 and chromone-pyrazolone 116 was synthesized from multifluorinated pyrazolone by the Knoevenagel condensation reaction. All compounds were synthesized by conventional heating as well as ultrasound irradiation technique. It was found that ultrasonication method was more efficient than conventional heating method.
SCHEME 6: SYNTHESIS OF MULTIFLUORINATED PYRAZOLONE CONTAINING PYRAZOLE AND CHROMONE
Pharmacological Properties: On the basis of various literature surveys pyrazolone derivatives shows various pharmacological activities.
CONCLUSION: On the basis of literature survey, pyrazolone derivatives exhibits antimicrobial, anti-inflammatory, analgesic, anticancer and antitubercular activities. This review gives an overview of various synthetic routes used to form a biologically rich pyrazolone moiety. The possible improvements in the activity can be further achieved by slight modifications in the substituents on the basic pyrazolone nucleus. This article proves to be helful for further research work on the bioactive pyrazolone ring and as an important tool for the development of better medicinal agents.
ACKNOWLEDGEMENT: We are grateful are due to the Head, School of studies in Chemistry and Central Library of Jiwaji University, Gwalior, India for providing necessary facility and support of this work.
REFERANCES:
- Mariappan G, Saha BP, Sutharson L, Garg S, Pandey L, Kumar D and Ankit S : The diverse pharmacological importance of pyrazolone derivatives. Journal of Pharmacy Research 2010; 3:2856-2859.
- Micha L: Hypersensitivity to pyrazolones. Thorax 2000; 55:S72–S74.
- Arnost M, Pierce A, Haar E, Lauffer D, Madden J, Tanner K and Green J : 3-Aryl-4-(arylhydrazono)-1H-pyrazol-5-ones: Highly ligand efficient and potent inhibitors of GSK3beta. Bioorganic and Medicinal Chemistry Letters 2010; 20:1661-1664.
- Kawai H, Nakai H, Suga M, Yuki S, Watanabe T and Saito KI : Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in the rat distal middle cerebral artery occlusion model. Jouranal of Pharmacoogical Experimental Therapeutics 1997; 281:921-927.
- Gursoy A, Demirayak S, Capan G, Erol K and Vural K : Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents. European Journal of Medicinal Chemistry 2000; 35:359-364.
- Castagnolo D, Manetti F, Radi M, Bechi B, Pagano M, Logu AD, Meleddu R, Saddi M and Botta M : Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: Part 2. Synthesis of rigid pyrazolones. Bioorganic and Medicinal Chemistry 2009; 17:5716-5721
- Parekh N, Maheria K, Patel P and Rathod M : Study on antibacterial activity for multidrug resistance stain by using phenyl pyrazolones substituted 3-amino 1H-pyrazolon (3,4-b) quinoline derivative in-vitro condition. International Journal of PharmTech Reasearch 2011; 3: 540-548..
- Mariappan G, Saha BP, Sutharson L and Haldar A : Synthesis and bioactivity evaluation of pyrazolone derivatives. Indian Journal of Chemistry 2010; 49:1671-1674
- Manojkumar P, Ravi TK and Subbuchettiar G : Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells. Acta Pharmaceutica 2009; 59:159-170.
- Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H and Ebner C : IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. Jouranal of Allergy and Clinical Immunology 2003; 111:882-888.
- Kakiuchi Y, Sasaki N, Satoh-Masuoka M, Murofushi H and Murakami-Murofushi K : A novel pyrazolone, 4,4-dichloro-1-(2,4-dichlorophenyl)-3-methyl-5-pyrazolone, as a potent catalytic inhibitor of human telomerase. Biochemical and Biophysical Research Communication 2004; 320:1351-1358.
- Wu TW, Zeng LH, Wu J and Fung KP : Myocardial protection of MCI-186 in rabbit ischemia-reperfusion. Life Science 2002; 71:2249-2255.
- Prasad YR, Rao AL, Prasoona L, Murali K and Kumar PR : Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2''-hydroxy naphthalen-1''-yl)-1,5-diphenyl-2-pyrazolines. Bioorganic and Medicinal Chemistry Letters 2005; 15:5030-5034.
- (a) Walker JR, Fairfull-Smith KE, Anzai K, Lau S, White PJ, Scammells PJ and Bottel SE : Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia. Medicinal Chemistry Communication 2011; 2:436-441. (b) Watanabe T, Yuki S, Egawa M and Nishi H: Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. Jouranal of Pharmacoogical Experimental Therapeutics 1994; 268:1597-1604.
- Kuçukguze G, Rollas S, Erdeniz H, Kiraz M, Ekinci AC and Vidin A : Synthesis, characterization and pharmacological properties of some 4-arylhydrazono-2-pyrazoline-5-one derivatives obtained from heterocyclic amines. European Journal of Medicinal Chemistry 2000; 35:761-771.
- Venkata CSR and Rao VRA: A Facile One-Pot Expeditious Synthesis of Thiazolyl-pyrazolones. Phosphorus, Sulfur and Silicon and Related Elements 2011; 186:489-495.
- For novel green methodologies, see: (a) Jia X, Duan H, Lin Y, Cao J, Liang D and Wu M : One-pot three-component synthesis of 4,4’-Arylidene-bis(3-methyl-pyrazolones) derivatives in water. Chemical Research in Chinese Universities 2012; 28:999-1002. (b) Tu X, Feng H, Tu M, Jiang B, Wang S and Tu S : Multicomponent domino reactions of acetylenedicarboxylates: divergent synthesis of multi-functionalized pyrazolones and C-tethered bispyrazol-5-ols. Tetrahedron Letters 2012; 53:3169-3172.
- Sujatha K, Shanthi G, Selvam NP, Manoharan S, Perumal PT and Rajendran M : Synthesis and antiviral activity of 4,40-(arylmethylene)bis(1H-pyrazol-5-ols) against peste des petits ruminant virus (PPRV). Bioorganic & Medicinal Chemistry Letters 2009; 19:4501–4503.
- Liu H, Guo J, Jia D, Guo M, Le F, Liu L, Wu D and Li F : Modulation of a solid-state reversible fluorescent photo switching based on a controllable photochromic pyrazolones. Journal of Solid State Chemistry 2014; 216:73–78.
- Baciu-Atudosie L, Ghinet A, Belei D, Gautret P, Rigo B and Bicu E : An efficient one-pot reaction for the synthesis of pyrazolones bearing a phenothiazine unit, Tetrahedron Letters 2012; 53:6127–6131.
- Manojkumar P, Ravi TK and Gopalakrishnan S: Antioxidant and antibacterial studies of arylazopyrazoles and arylhydrazonopyrazolones containing coumarin moiety. European Journal of Medicinal Chemistry 2009; 44:4690–4694.
- Gunasekaran P, Perumal S, Yogeeswari P and Sriramb D: A facile four-component sequential protocol in the expedient synthesis of novel 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones in water and their antitubercular evaluation. European Journal of Medicinal Chemistry 2011; 46:4530-4536.
- Shah PJ, Patel BP and Patel HS: Synthesis, Characterization and antibacterial activity of novel pyrazolone derivatives. Journal of the University of Chemical Technology and Metallurgy 2012; 47:257-262.
- Mosaddegh E, Islami MR and Shojaie Z: A clean and highly efficient synthesis of 4,4’-(arylmethylene) bis (3-methyl-1-phenyl-1H-pyrazol-5-ols) using Ce(SO4)2.4H2O as heterogeneous catalyst. Arabian Journal of Chemistry 2013; DOI: 10.1016/j.arabjc.2013.02.016.
- Ahmad A, Varshney H, Rauf A, Husain FM and Ahmad I : Synthesis, biological screening of novel long chain derivatives of 1,3-disubstituted-1H-pyrazol-5(4H)-one and 2-substituted-3H-1,4-phthalazin-1,4-dione: Structure-activity relationship studies, Journal of King Saud University – Science 2014; 26:290-299
- Ragavan RV, Vijaykumar V and Suchetha Kumari N : Synthesis of some novel bioactive 4-oxy/thio substituted-1H-pyrazol-5(4H)-ones via efficient cross-Claisen condensation. European Journal of Medicinal Chemistry 2009; 44:3852-3857.
- Konkov SA and Moiseev IK : Synthesis of Pyrazoles and Pyrazolones from 1,3- and 1,4- Diketones of the Adamantane Series. Russian Journal of Organic Chemistry 2009; 45:1824–1828.
- Bran MF, Gradillas A, Ovalles AG, Lopez B, Acero N, Llinaresc F and Mingarroa DM : Synthesis and biological activity of N,N-dialkylaminoalkyl substituted bisindolyl and diphenyl pyrazolone derivatives. Bioorganic & Medicinal Chemistry 2006; 14:9–16.
- Burja B, Cimbora-Zovko T, Tomic S, Jelusic T, Kocevar M, Polanc S and Osmak M : Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies. Bioorganic & Medicinal Chemistry 2010; 18:2375–2387.
- Shamsuzzamana, Dara AM, Shervanib S, Bhatc I, Gatoo MA : Structural, optical and antimicrobial studies of 3-acetoxycholest-5-ene, 3β-acetoxy-6-nitrocholest-5-ene and newly synthesized steroidal pyrazolones. Journal of Taibah University for Science 2014; 8:39–53.
- Laufersweiler MJ, Brugel TA, Clark MP, Golebiowski A, Bookland RG, Laughlin SK, Sabat MK, Townes JA, VanRens JC, De B, Hsieh LC, Heitmeyer SA, Juergens K, Brown KK, Mekel MJ, RLWalter and Janusz MJ. The development of novel inhibitors of tumor necrosis factor-a (TNF-a) production based on substituted [5,5]-bicyclic pyrazolones. Bioorganic & Medicinal Chemistry Letters 2004; 14:4267–4272.
- Tripathy R, Ghose A, Singh J, Bacon ER, Angeles TS, Yang SX, Albom MS, Aimone LD, Herman JL and Mallamo JP : 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors. Bioorganic & Medicinal Chemistry Letters 2007; 17:1793–1798.
- Huang Y, Lin H, Cheng K, Su W, Sung K, Lin T, Huang J, Lin S and Wong F : Efficient di-bromination of 5-pyrazolones and 5-hydroxypyrazoles by N-bromobenzamide. Tetrahedron 2009; 65:9592–9597.
- Kadam A, Dawane B, Pawar M, Shegokar H, Patil K, Meshram R and Gacche R : Development of novel pyrazolone derivatives as inhibitors of aldose reductase: An eco-friendly one-pot synthesis, experimental screening and in silico analysis. Bioorganic Chemistry 2014; 53:67–74
- Mehta HB, Patel PK, Dixit BC and Dixit RB: Synthesis and antimicrobial activities of new mono and bisphenyl linked bispyrazole and bispyrazolone derivatives. Arabian Journal of Chemistry 2013; DOI: 10.1016/j. arabjc. 2013.07.019.
- Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR: Vogel’s textbook of practical organic Chemistry, 5th ed. Pearson Education (Singapore) Pvt. Ltd., Delhi, India, 2004.
- Ghosh PP, Pal G, Paul S and Das AR: Design and synthesis of benzylpyrazolyl coumarin derivatives via a four component reaction in water: investigation of the weak interactions accumulating in the crystal structure of a signified compound. Green Chemistry 2012; 14:2691–2698.
- Tu X, Feng H, Tu M, Jiang B, Wang S and Tu S : Multicomponent domino reactions of acetylenedicarboxylates: divergent synthesis of multi-functionalized pyrazolones and C-tethered bispyrazol-5-ols. Tetrahedron Letters 2012; 53:3169–3172.
- Sivakumar KK, Rajasekaran A, Senthilkumar P and Wattamwar PP: Conventional and microwave assisted synthesis of pyrazolone Mannich bases possessing anti-inflammatory, analgesic, ulcerogenic effect and antimicrobial properties. Bioorganic & Medicinal Chemistry Letters 2014; 24:2940–2944.
- Antre RV, Cendilkumar A, Goli D, Andhale GS and Oswal RJ: Microwave assisted synthesis of novel pyrazolone derivatives attached to a pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and antipyretic activities. Saudi Pharmaceutical Journal 2011; 19:233–243.
- Zang H, Su Q, Mo Y and Cheng B: Ionic liquid under ultrasonic irradiation towards a facile synthesis of pyrazolone derivatives. Ultrasonics Sonochemistry 2011; 18:68–72.
- Ziarati A, Safaei-Ghomi J and Rohani S: Sonochemically synthesis of pyrazolones using reusable catalyst CuI nanoparticles that was prepared by sonication. Ultrasonics Sonochemistry 2013; 20:1069–1075.
- Gadhave A, Kuchekar S and Karale B: Ultrasonication-Induced Synthesis and antimicrobial evaluation of some multifluorinated pyrazolone derivatives. Journal of Chemistry 2013; 2013: 9 pages
- Indrasena A, Riyaz SD, Mallipeddi L, Padmaja P, Sridhar B and Dubey PK : Design, synthesis, and biological evaluation of indolylidinepyrazolones as potential anti-bacterial agents. Tetrahedron Letters 2014; 55:5014-5018.
- Rasapalli S, Fan Y, Yu M, Rees C, Harris JT, Golen JA, Jasinski JP, Rheingold AL, Kwasny SM and Opperman TJ: Detour of prenostodione synthesis towards pyrazolones for antibacterial activity. Bioorganic & Medicinal Chemistry Letters 2013; 23:3235–3238.
- Kaczor AA, Wrobel T, Karczmarzyk Z, Wysocki W, Mendyk E, Poso A, Matosiuk D and Pitucha M : Experimental and computational studies on the tautomerism of N-substituted 3-amino-5-oxo-4-phenyl-1H-pyrazolo-1-carboxamides with antibacterial activity. Journal of Molecular Structure 2013; 1051:188–196.
- Saidachary G, K. Prasad KV, Divyab D, Singh A, Ramesh U, Sridhar B, Raju BC : Convenient one-pot synthesis, anti-mycobacterial and anticancer activities of novel benzoxepinoisoxazolones and pyrazolones. European Journal of Medicinal Chemistry 2014; 76:460-469.
- Mariappan G, Saha BP, Sutharson L, Singh A, Garg S, Pandey L and Kumar D : Analgesic, anti-inflammatory, antipyretic and toxicological evaluation of some newer 3-methyl pyrazolone derivatives. Saudi Pharmaceutical Journal 2011; 19:115–122.
- Al-Tel TH, Semreen MH and Voelter W: Tandem Achmatowicz-Knoevenagel protocol: diastereo selective synthesis and anticancer evaluation. ofcyclopenta [b] pyrane Organic and Biomolecular Chemistry 2010; 8:5375-5382.
- Gouda MA, Eldien HF, Girges MM and Berghot MA: Synthesis and antitumor evaluation of thiophene based azo dyes incorporating pyrazolone moiety. Journal of Saudi Chemical Society 2012; DOI: 10.1016/j.jscs.2012.06.004
- Zhang Y, Zhang L, Liu L, Guo J, Wua D, Xu G, Wang X and Jia D : Anticancer activity, structure, and theoretical calculation of N-(1-phenyl-3-methyl-4-propyl-pyrazolone-5)-salicylidene hydrazone and its copper(II) complex. Inorganica Chimica Acta 2010; 363:289–293.
- Chopde HN, Meshram JS and Pagadala RK: Synthesis, characterization and antibacterial evaluation of some azetidinone derivatives of 3-methyl-1H-pyrazol-5(4H)-one. Archives of Applied Science Research 2012; 4:1442-1446.
- Srivalli T, Satish K and Suthakaran R: Synthesis, characterisation and analgesic evaluation of some pyrazolone derivatives. International Journal of Innovative Pharmaceutical Research 2011; 2:172-174.
- Castagnolo D, Logu AD, Radi M, Bechi B, Manetti F, Magnani M, Supino S, Meleddu R, Chisu L and Botta M : Synthesis, biological evaluation and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis. Bioorganic & Medicinal Chemistry 2008; 16:8587–8591.
- Chen T, Benmohamed R, Arvanites AC, Ranaivo HR, Morimoto RI, Ferrante RJ, Watterson DM, Kirsch DR and Silverman RB : Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis. Bioorganic & Medicinal Chemistry 2011; 19:613–622.
- El-Borai MA, Rizk HF, Beltagy DM and El-Deeb IY: Microwave-assisted synthesis of some new pyrazolopyridines and their antioxidant, antitumor and antimicrobial activities. European Journal of Medicinal Chemistry 2013; 66:415-422.
- Kondaskar A, Kondaskar S, Fishbein JC, Carter-Cooper BA, Lapidus RG, Sadowska M, Edelman MJ and Hosmane RS : Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:40,50-f][1,3]diazepines. Bioorganic & Medicinal Chemistry 2013; 21:618–631
How to cite this article:
Gupta P, Gupta JK and Halve AK: Synthesis and Biological Significance of Pyrazolones: A Review. Int J Pharm Sci Res 2015; 6(6): 2291-10.doi: 10.13040/IJPSR.0975-8232.6(6).2291-10.
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Article Information
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2291-10
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English
Ijpsr
Poonam Gupta*, Jitendra K. Gupta and A. K. Halve
School of studies in Chemistry, Jiwaji University, Gwalior-474011, Madhya Pradesh, India
poonamgupta_001@yahoo.com
01 October, 2014
08 January, 2015
27 March, 2015
10.13040/IJPSR.0975-8232.6(6).2291-10
01 June, 2015