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| REVIEW ARTICLE |
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| Year : 2016 | Volume
: 8
| Issue : 1 | Page : 2-17 |
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Current status of pyrazole and its biological activities
Mohd Javed Naim1, Ozair Alam1, Farah Nawaz1, Md. Jahangir Alam1, Perwaiz Alam2
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Shree Ganpati Institute of Technology, Ghaziabad, Uttar Pradesh, India
| Date of Submission | 24-Apr-2015 |
| Date of Decision | 27-Jul-2015 |
| Date of Acceptance | 20-Aug-2015 |
| Date of Web Publication | 13-Jan-2016 |
Correspondence Address:
Ozair Alam
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0975-7406.171694
 Abstract | | |
Pyrazole are potent medicinal scaffolds and exhibit a full spectrum of biological activities. This review throws light on the detailed synthetic approaches which have been applied for the synthesis of pyrazole. This has been followed by an in depth analysis of the pyrazole with respect to their medical significance. This follow-up may help the medicinal chemists to generate new leads possessing pyrazole nucleus with high efficacy.
Keywords: Anti-microbial, hetrocyclic and biological activity, pyrazole
How to cite this article:
Naim MJ, Alam O, Nawaz F, Alam MJ, Alam P. Current status of pyrazole and its biological activities. J Pharm Bioall Sci 2016;8:2-17 |
Pyrazole is a five-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions as represented by the molecular formula C3H4N2. It is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25°C). The term pyrazole was first coined by Ludwig Knorr in 1883. Due to its composition and unique pharmacological effects on human beings, they are classified as alkaloids. 1-pyrazolyl-alanine was the first natural pyrazole isolated from watermelon seeds in the year 1959.[1],[2]
Pyrazoles are reported to possess a wide range of biological activities in literature such as anti-microbial, anti-fungal, anti-tubercular, anti-inflammatory, anti-convulsant, anticancer, anti-viral, angiotensin converting enzyme (ACE) inhibitory, neuroprotective, cholecystokinin-1 receptor antagonist, and estrogen receptor (ER) ligand activity, etc. which are as shown in [Figure 1].[3] Many pyrazole derivatives has already found their application as nonsteroidal anti-inflammatory drugs clinically, such as anti-pyrine or phenazone (analgesic and antipyretic), metamizole or dipyrone (analgesic and antipyretic), aminopyrine or aminophenazone (anti-inflammatory, antipyretic, and analgesic), phenylbutazone (anti-inflammatory, antipyretic mainly used in osteoarthritis, rheumatoid arthritis, spondylitis, Reiter's disease), sulfinpyrazone (chronic gout), and oxyphenbutazone (antipyretic, analgesic, anti-inflammatory, mild uricosuric).[4] In this review, our main intention is to emphasize on the different biological activities exhibited by pyrazole moiety. Marketed drugs containing pyrazole moiety are as shown in [Figure 2].
| Synthetic Aspects of Pyrazole | |  |
- Synthesis of 1, 3-substituted pyrazolesAn iron-catalyzed route for the regioselective synthesis of 1,3- and 1, 3, 5-substituted pyrazoles from the reaction of diarylhydrazones and vicinal diols [Figure 3][5]
- Synthesis of tri- and tetra-substituted pyrazolesA ruthenium (II)-catalyzed intramolecular oxidative CN coupling method for the facile synthesis of a tri- and tetra-substituted pyrazoles. Dioxygen gas is employed as the oxidant in this transformation and the reaction demonstrates excellent reactivity, functional group tolerance, and high yields [Figure 4][6]
- Synthesis of 3,5-substituted-1H-pyrazoleA novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of α, β-unsaturated carbonyl compounds possessing a β-hydrogen is proposed, exploiting microwave activation coupled with solvent free reaction conditions [Figure 5][7]
- Synthesis of 3-benzofuran-2-yl-1-p-tolyl-1H-pyrazoleThe 2-acyl benzofurohydrazones subjected to Vilsmeier–Haack reaction that is reaction with N, N-dimethylformamide (DMF)/POCl3 at an appropriate molar ratio, which underwent smooth cyclization followed by formylation afforded 3-(1-benzofuran-2-yl)-1-(4-fluorophenyl)-1H-pyrazole-4-carbaldehyde [Figure 6][8]
- Synthesis of 1-(4,5-disubstitutedpyrazol-1-yl)-ethanoneA novel one-pot synthesis of pyrazoles has been accomplished by the reaction of β-formyl enamides with hydroxylamine hydrochloride catalyzed by potassium dihydrogen phosphate in acidic medium [Figure 7][9]
- Synthesis of 1, 3, 5-trisubstituted-1H-pyrazoleThe reaction of the easily accessible 1, 3-bisaryl-monothio-1,3-diketone or 3-(methylthio)-1,3-bisaryl-2-propenones with arylhydrazines gives 1-aryl-3,5-bisarylpyrazoles with complementary regioselectivity at position 3 and 5 [Figure 8].[10]
 | Figure 6: Synthesis of 3-benzofuran-2-yl-1-p-tolyl-1H-pyrazole derivatives
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Pharmacological activity
For a very long time, the usefulness and great therapeutic value of pyrazole nucleus have been recognized and widest range of activities of this nucleus evaluated. However, as the first synthetic organic compound having pyrazoline-5-one nucleus, to find use as an important drug. Phenylbutazone as a prototype of pyrazolidinedione is a very potent anti-inflammatory agent, but its use is now banned in some countries. Later on, many modifications of pyrazole nucleus were attempted and several compounds have been synthesized which serves as the basis for the treatment of different diseases like-inflammation, pain, cancer, tuberculosis, and diseases caused by bacteria.
Anti-inflammatory activity
Kendre et al.,[11] have synthesized a new series of pyrazole, isoxazole, benzoxazepine, benzothiazepine, and benzodiazepine derivatives by the multi-component cyclo-condensation reaction of 1-phenyl-3-(2-(tosyloxy)phenyl)propane-1,3-dione, DMF dimethyl acetal, and hydrazine or hydroxylamine hydrochloride or 2-aminothiophenol or 2-aminophenol or benzene-1,2-diamine by MW technique in aqueous media. Compound 3a screened for their anti-inflammatory activity using indomethacin as the standard drug was found to be potent [Figure 9].
Tewari et al.,[12] have synthesized a novel series of pyrazole derivatives and evaluated in vivo for their anti-inflammatory activity in carrageenan-induced rat paw edema model using nimesulide as the standard drug. Molecular modeling studies showed that pyrazole analogs interact with cyclooxygenase-2 (COX-2) active site by forming classical hydrogen bonding, π-π interaction, and cation–π interaction which increases the residence of ligand in the active site consequently augmenting anti-inflammatory activity of compounds. Compound 5b was found to be most potent [Figure 10].
Alegaon et al.,[13] have synthesized 22 1, 3, 4-trisubstituted pyrazole derivatives and structure of newly synthesized compounds were characterized by infrared (IR),1 H nuclear magnetic resonance (NMR),13 C NMR, and mass spectral analysis. These compounds were screened for the anti-inflammatory activity by carrageenan-induced paw edema method. Compounds 5a showed excellent anti-inflammatory activity (≥84.2% inhibition) as compared to that of the standard drug diclofenac (86.72%) when measured 3 h after the carrageenan injection [Figure 11].
Sharath et al.,[14] have synthesized substituted indole based scaffolds having a pyrazole ring and evaluate for their anti-inflammatory activity and antioxidant. The structures of newly synthesized compounds were elucidated by spectroscopic methods such as IR,1 H NMR,13 C NMR, mass, and elemental analysis. Compound 7c exhibits a promising anti-inflammatory activity using indomethacin as the standard drug [Figure 12]. | Figure 12: Synthesized substituted indole based scaffolds having a pyrazole ring
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Thoreet al.,[15] have reported the synthesis of a novel series of ethyl-5-amino-3-methylthio-1H-pyrazole-4-carboxylates from the condensation of various hydrazides with ketene dithioacetal. Compounds 3a exhibited significant anti-inflammatory activity at a dose of 25 mg/kg using diclofenac sodium as the standard drug [Figure 13]. | Figure 13: Synthesis of a novel series of ethyl-5-amino-3-methylthio-1H-pyrazole-4-carboxylates
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Bandgar et al.,[16] have synthesized a series of novel pyrazole integrated benzophenones from 1-methyl-5-(2, 4, 6-trimethoxy-phenyl)-1H-pyrazole. All the compounds were proved as marked anti-inflammatory potential against various inflammatory mediators. Among the synthesized compounds, 9b, 9d, and 9f, were found to be active anti-inflammatory agents using indomethacin as the standard drug [Figure 14]. | Figure 14: Synthesis of benzophenones from 1-methyl-5-(2, 4, 6-trimethoxyphenyl)-1H-pyrazole
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Kecheet al.,[17] have synthesized a series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reaction of resulting amine with different aryl isocyanates or arylisothiocyanates or aryl sulfonyl chlorides. Compounds 4 and 16 found to have promising anti-inflammatory activity (up to 61–85% tumor necrosis factor [TNF-α] and 76–93% interleukin-6 [IL-6] inhibitory activity) at concentration of 10 lM with reference to the standard drug dexamethasone (76% TNF-α and 86% IL-6 inhibitory activity at 1 lM) [Figure 15]. | Figure 15: Synthesized a series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives
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Selvamet al.,[18] have synthesized a series of 1-(4-substitutedphenyl)-3-phenyl-1H-pyrazole-4-carbaldehydes and tested for their anti-inflammatory activities. 4g, 4i, and 4k exhibited maximum activity as compared to the standard drug diclofenac sodium [Figure 16]. | Figure 16: Synthesis of 1-(4-substitutedphenyl)-3-phenyl-1H-pyrazole-4-carbaldehydes
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El-Sayedet al.,[19] have synthesized new pyrazole derivative characterized as N-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)-3,5 bis(trifluoromethyl)aniline (8d) which exhibited optimal anti-inflammatory activity as comparable with reference drugs diclofenac sodium and celecoxib [Figure 17]. | Figure 17: Synthesis of N-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)-3,5bis(trifluoromethyl)aniline
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Nagarapuet al.,[20] have synthesized a new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl) propyl]-1H-pyrazole-5-carboxamide derivatives. All compounds were investigated using carrageenan-induced rat paw edema model in vivo using ibuprofen as the standard. Four derivatives 10a, 10e, 10f, and 10g were found to be more potent at 3 h (75%, 70%, 76%, and 78%, respectively) [Figure 18]. | Figure 18: Synthesis of 3-phenyl-N-[3-(4-phenylpiperazin-1yl) propyl]-1H-pyrazole-5-carboxamide derivatives
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Bandgaret al.,[21] have synthesized a series of 3,5-diaryl pyrazole derivatives characterized as 2-[5-(2-chloro-phenyl)-1H-pyrazol-3-yl]-6-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-3,5-dimethoxy-phenol using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate. The compounds 2a, 2c, 2d, and 2i give IL-6 inhibitory activity while 2a and 2d inhibit TNF-α actively [Figure 19]. | Figure 19: 2-[5-(2-chloro-phenyl)-1H-pyrazol-3-yl]-6-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-3,5-dimethoxy-phenol
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Bekhit et al.,[22] have synthesized a series of 4-thiazolyl pyrazolyl and studied there COX-1, COX-2 ulcerogenic effect, and acute toxicity, in vitro anti-microbial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. All compounds were examined for their anti-inflammatory activity using cotton pellet-induced granuloma and carrageenan-induced rat paw edema bioassays. Compounds 10a and 10b were found to be the most potent anti-inflammatory agents using indomethacin as the standard drug [Figure 20].
Chandra et al.,[23] have reported a series of compounds with anti-inflammatory and analgesic activities. The compound (24) 1-(2, 4-Chloroacridine-9-yl)-3-(5-pyridine-4-yl)-(1, 3, 4-oxadiazol-2-yl-thiomethyl)-pyrazole-5-one showed better anti-inflammatory and analgesic activities at the three graded doses of 25, 50, and 100 mg/kg p.o using phenylbutazone as the standard drug [Figure 21]. | Figure 21: Synthesis of 1-(2, 4-Chloroacridine-9-yl)-3-(5-pyridine-4-yl)-(1,3,4-oxadiazol-2-yl-thiomethyl)-pyrazole-5-one
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Bandgaret al.,[24] have synthesized novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone by the Claisen–Schmidt condensation of 1-(2,4-dimethoxy-phenyl)-ethanone and substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes. All the synthesized compounds were evaluated for anti-inflammatory activity by TNF-α and IL-6 inhibition assays. Compounds 3a, 3c, and 3g exhibited promising IL-6 inhibitory activity using dexamethasone as the standard drug [Figure 22]. | Figure 22: Synthesis of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone
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Abdel-Hafezet al.,[25] have prepared novel pyrazole-NO hybrid molecules and evaluated them for nitric oxide release, anti-bacterial, and anti-inflammatory activities. The organic nitrate ester 10 was found to be most active as compared to the standard drug indomethacin [Figure 23].
Barsoum and Girgis,[26] have prepared a series bis (3-aryl-4, 5-dihydro-1H-pyrazole-1-thiocarboxamides) and bis (3-aryl-4, 5-dihydro-1H-pyrazole-1-carboxamides). Synthesized compounds were tested for anti-inflammatory activity in carrageenan-induced paw edema method in rats. The compounds 2e and 2f were found to be most potent relative to indomethacin [Figure 24].
Bekhit et al.,[27] have synthesized a series of N, N-Dimethylaminomethylene-4-[3-phenyl-4-(3-substituted-4-oxothiazolidin-2-ylidenehydrazonomethyl)-1H-pyrazolyl] derivatives. All the target compounds showed good anti-inflammatory activity and 3b and 3c have surpassed that of indomethacin both locally and systemically [Figure 25]. | Figure 25: N,NDimethylaminomethylene-4-[3-phenyl-4-(3-substituted-4-oxothiazolidin-2 ylidenehydrazonomethyl)-1H-pyrazolyl] derivatives
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Gökhan-Kelekçi et al.,[28] have synthesized a novel series of 1-thiocarbamoyl 3-substituted phenyl-5-(2-pyrrolyl)-4, 5-dihydro-(1H)-pyrazole derivatives as promising monoamine oxidase B (MAO-B) inhibitor. Few synthesized compounds showed high activity against both the MAO-A and MAO-B isoforms. They also tested synthesized compound for their anti-inflammatory activity against carrageenan-induced edema and an acetic acid-induced increase in capillary permeability in mice. The compound 3k exhibit anti-inflammatory (comparable to indomethacin), analgesic, and MAO-B inhibitory activity [Figure 26]. | Figure 26: 1-thiocarbamoyl 3-substituted phenyl-5-(2-pyrrolyl)-4,5-dihydro-(1H)-pyrazole derivatives
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Burguete et al.,[29] has synthesized novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogs and evaluated them for their anti-inflammatory activities. Compound 2a was found to be most potent against carrageenan induced rat paw edema test using indomethacin as the standard drug [Figure 27]. | Figure 27: Substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives
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Bekhit and Abdel-Aziem [30] have synthesized 3-(5-Bromo-2-thienyl)-4-[1-phenylthiocarbamoyl-3-(4-methylphenyl)-2-pyrazolin-5-yl]-1-phenyl-1H-pyrazole from a novel series of structurally related 1H-pyrazolyl derivatives and these compounds were tested for their in vivo anti-inflammatory activity by cotton pellet-induced granuloma and sponge implantation model of inflammation in rats. Compound 12a was found to be most potent using indomethacin as the standard [Figure 28]. | Figure 28: Synthesized 3-(5-Bromo-2-thienyl)-4-[1-phenylthiocarbamoyl-3-(4-methylphenyl)-2-pyrazolin-5-yl]-1-phenyl-1H-pyrazole
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Balsamoet al.,[31] have synthesized several hetero-aromatic analogs of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors, in which the cyclopentene moiety was replaced by pyrazole, proved to be significantly active only toward the COX-1. Compounds 12 and 16 were found to be active [Figure 29].
Anti-microbial, anti-tubercular, and anti-fungal activity
Ahsan and Saini,[32] have designed and synthesized a series of thiocetazone based pyrazoline analogs by the condensation of 4-aminoacetophenone and p-anisidine in methanolic sodium hydroxide solution followed by the cyclization of intermediate chalcone with appropriate semicarbazide/thiosemicarbazide in glacial acetic acid. All the synthesized compounds were characterized by 1 H NMR, IR, and mass spectral data and the purity of the compounds was checked by elemental analysis. Compound 4i showed maximum activity against Mycobacterium tuberculosis (MTB H37Rv) with minimum inhibitory concentration (MIC) of 7.41 mM [Figure 30].
Pathak et al.,[33] have synthesized various substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2-(heteroaryl)pyrimidine and 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)ethanone in good yields and evaluated them for their in vitro anti-tubercular activity against MTB H37Rv strain. Compounds 7b and 7c were found to be active [Figure 31]. | Figure 31: Substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2-(heteroaryl) pyrimidine
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Maurya et al.,[34] have synthesized various substituted 5,6-dihydro-8-methoxybenzo[h]quinazolin-2-amine, 1-(3-(4-alkoxyphenyl)-7-methoxy-3,3a, 4, 5-tetrahydro-2H benzo[g]indazol-2 yl)ethanone, pyrazole, and 2,6-diarylpyridine derivatives in good yields and evaluated them for their in vitro anti-tubercular activity against MTB H37Rv strain. Compound 19a was found to be potent and safe [Figure 32].
Ahsan et al.,[35] has synthesized a series of 3a,4-dihydro-3H-indeno [1,2-c]pyrazole-2-carboxamide/carbothioamide analogs and evaluated them for anti-tubercular activity. Compound 4o showed low to high inhibitory activities against MTB H37Rv and INH resistant MTB with MIC 3.12 lM and 6.25 lM, respectively [Figure 33].
Bondock et al.,[36] have synthesized a series of fused pyrazole-pyrimidine derivatives. The compound 21b was found to exhibit the most potent in-vitro anti-fungal activity with MICs (6.25 μ/ml) against Aspergillus fumigatus and Fusarium oxysporum comparable with chloroamphenicol [Figure 34].
Ragavanet al.,[37] have synthesized a group of novel 1,5-diaryl pyrazole by altering the active part (amide linkage) and tested for anti-bacterial activity against E. coli (American Type Culture Collection [ATTC] - 25922), S. aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC-27853), Klebsiella pneumonia. Compound 11 showed good activity and further studies revealed that the aliphatic amide pharmacophore is important for the anti-microbial activities of studied pyrazole; especially the presence of 4-piperidine moiety enhances the activity [Figure 35].
Argadeet al.,[38] have reported the synthesis of pyrazole containing 2,4-disubstituted oxazol-5-one as a new class of anti-microbial compounds. Compound 3d showed the highest activity against ampicillin and ketoconazole as standard drugs [Figure 36].
Chovatiaet al.,[39] have reported the synthesis of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives and these compounds were tested in vitro for their anti-tubercular and anti-microbial properties. All the compounds were screened against MTB strain H37Rv at a concentration of 6.25 µg/mL in BACTEC 12B medium using the ALAMAR radiometric system and were compared against the standard drug rifampin at 0.25 µg/mL concentrations, which showed 98% inhibition. The anti-microbial activity was done against the bacterial strains Bacillus coccus, Bacillus subtilis, E. coli, Proteus vulgaris, and the fungi Aspergillus niger at a concentration of 40 µg/mL using ampicillin, amoxicillin, norfloxacin, benzyl penicillin, and griseofulvin as standard drugs. Compound 4b showed promising results [Figure 37].
Rai and Kalluraya [40] have reported novel series of nitrofuran containing 1, 3, 4, 5 tetrasubstituted pyrazole derivatives. The compound showed good anti-bacterial and anti-fungal activity. The anti-bacterial activity was studied on E. coli, P. aeruginosa, S. aureus, and B. subtilis using furacin as the standard drug. The anti-fungal activity was studied on C. albicans using fluconazole as the standard drug. Compound 3b showed promising results [Figure 38].
Neuroprotective activity
Cocconcelli et al.,[41] have described the parallel synthesis of aryl azoles. Here substituted hydrazine is made to react with α-β-unsaturated ketones in the presence of a catalyst (acetic acid), which leads to the regioselective formation of 4,5-dihydro-1-H-pyrazole. All compounds obtained were evaluated in an in vitro assay using an N-methyl-D-aspartate toxicity paradigm showing a neuroprotective activity between 15% and 40%. Compound 3a showed good activity [Figure 39].
Estrogen receptor ligands
Naoum et al.,[42] has synthesized novel tetra-substituted pyrazole derivatives bearing a nitro substituent on their phenol ring and their binding affinity toward the ER subtypes ERα and ERβ was determined. Compound 5c was found to be active [Figure 40].
Cholecystokinin-1 receptor antagonists
Gomezet al.,[43] have reported the synthesis and structure-activity relationship studies of 1,5-diarylpyrazoles analogs with various structural modifications of the alkane side chain of the molecule and concluded that compound showed good oral bioavailability and could be used for the potential treatments of irritable bowel syndrome and other gastrointestinal disorders. Compound 19 showed good results [Figure 41].
Anticonvulsant and antidepressant activity
Ahsan [44] has synthesized 3-substituted-N-aryl-6,7-dimethoxy-3a,4-dihydro-3H-indeno [1,2-c]pyrazole-2-carboxamide and the anticonvulsant activity and neuroprotection assay were done according to Antiepileptic Drug Development Programme protocol. Compound 4b showed neuroprotection activity with 26.2 ± 1.9% of total propidium iodide uptake at 100 µM and inhibitory concentration 50 (IC50) of the compound was found to be 159.20 ± 1.21 µM [Figure 42]. | Figure 42: 3-substituted-N-aryl-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide
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Abdel-Azizet al.,[45] have described two synthetic paths for the formation of diacylhydrazines, 5amino-1-substiuted pyrazole-3, 3, 4-tricarbonitriles and oxadiazole, pyrazolone derivatives, showing antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against pentylenetetrazol induced seizures in mice. Compounds 4a and 4b showed good activity as compared to imipramine at a dose of 10 mg/kg dose level [Figure 43].
Chimenti et al.,[46] have synthesized a novel series of 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives and investigated their ability to selectively inhibit the activity of the isoforms of MAO. The newly synthesized compound proved to be more reversible, potent, and selective inhibitors of MAO-A than of MAO-B. Compounds 6 and 11 were found to be most potent [Figure 44]. | Figure 44: 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives
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Antiviral activity
el-Sabbagh et al.,[47] have synthesized 4, 5-disubstituted pyrazole derivatives. The derivative containing R=Cl group showed the potent antiviral activity against a broad panel of viruses in different cell culture (HEL cell cultures). Compound 7 was found to be most potent [Figure 45].
Rashad et al.,[48] have synthesized substituted pyrazole derivatives. These derivatives showed promising antiviral activity against hepatitis A virus and Herpes simplex virus type-1 using plaque infective assay. Compounds 1, 2, and 3 showed good activity against amantadine and acyclovir (used as controls) [Figure 46].
Angiotensin converting enzyme-inhibitory activity
Bonesi et al.,[49] have synthesized a series of pyrazole derivatives and investigated their potential activity as ACE inhibitory activity by performing the assay. One of the derivatives of pyrazole (15) showed effective ACE-inhibitory activity with 0.123 mM IC50 value [Figure 47].
Anticancer activity
Cankara Pirol et al.,[50] have synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and determined their anti-proliferative activities against three human cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines). Compound 4j with 2-chloro-4-pyridinyl group in the amide part showed good cytotoxic activity against all cell lines with IC50 values of 1.6 mM, 3.3 mM, and 1.1 mM for Huh7, MCF7, and HCT116 cells [Figure 48].
Ali et al.,[51] have synthesized a series of imidazo [2,1-b]thiazoles having pyrazole moieties through the reaction of 6-hydrazinylimidazo [2,1-b]thiazoles with different dicarbonyl compounds. The compounds were screened at the National Cancer Institute, USA for anticancer activity and 5a showed promising results [Figure 49]. | Figure 49: Synthesis of imidazo[2,1-b]thiazoles having pyrazole moieties
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Sangani et al.,[52] have synthesized a series of pyrazole quinolone-pyridine hybrids based on molecular hybridization technique and synthesized by a base-catalyzed cyclocondensation reaction through one-pot multicomponent reaction. All compounds were tested for in vitro anti-bacterial and anticancer activities of which 7k showed promising results [Figure 50].
Dawood et al.,[53] have synthesized N-(4-(Pyrazol-4-yl)thiazol-2-yl)-N0-phenylthiourea derivative and then treated with a variety of hydrazonoyl chlorides under basic condition (refluxed) to afford the corresponding 2-(4-(pyrazol- 4-yl)thiazol-2-ylimino)-1, 3, 4-thiadiazole derivatives. Compound 23d was found to be most potent as compared to the doxorubicin as the reference drug [Figure 51]. | Figure 51: N-(4-(Pyrazol-4-yl)thiazol-2- yl)-N0-phenylthiourea derivative
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Puthiyapurayilet al.,[54] have designed and synthesized a novel combinatorial library of S-substituted-1, 3, 4-oxadiazole bearing N-methyl-4-(trifluoromethyl) phenyl pyrazole moiety and then tested it for in-vitro cytotoxic activity by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Compound 5e showed good anticancer activity with IC50 value of 15.54 mM in MCF-7 cells, compared to doxorubicin as a standard drug [Figure 52]. | Figure 52: S-substituted-1,3,4-oxadiazole bearing N-methyl-4-(trifluoromethyl) phenyl pyrazole moiety
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Christodoulou et al.,[55] have synthesized a series of trisubstituted pyrazole derivatives and (Bis(trifluoroacetoxy)iodo)benzene-mediated conversion of molecules bearing the fused pyrazolo [4,3-c] quinolone ring system and evaluated them for anti-angiogenic activity by using in vitro assays for endothelial cell proliferation and migration, and the chicken chorioallantoic membrane assay. Compounds having fused pyrazolo [4,3-c] quinoline motifs emerged as potent anti-angiogenic compounds and inhibits the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro. Compound 8b was found to be most potent [Figure 53].
Lv et al.,[56] have designed two series of pyrazole derivatives and evaluated them for their potential epidermal growth factor receptor kinase inhibitors activity. Compound 3-(3, 4-dimethylphenyl)-5-(4-methoxy phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) is most potent with IC50 of 0.07 μM, as compared to positive control erlotinib [Figure 54]. | Figure 54: Synthesis of 3-(3,4-dimethylphenyl)-5-(4-methoxy phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide
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Niculescu-Duvaz et al.,[57] have synthesized a series of analogs leading to the discovery of 6-{2-[4-(4 methyl piperazin-1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno [1,2-c] pyrazole and carried out bioassay inhibition of purified mutant BRAF activity in vitro. Compound 1j was found to be most potent [Figure 55]. | Figure 55: 6-{2-[4-(4 methyl piperazin-1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno [1,2-c] pyrazole
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}
Insuastyet al.,[58] have synthesized novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (pyrazolicchalcones), among them some compound showed potent activity against leukemia (K-562 and SR), renal cancer (UO-31), and non-small cell lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 μ to 11.4 lμ, from the in vitro assays. Compound 5c was found to be most potent [Figure 56]. | Figure 56: (E)-1-aryl-3-(3-aryl-1- phenyl-1H-pyrazol-4-yl)prop-2-en-1-one(pyrazolicchalcones)
Click here to view |
Zhenget al.,[59] have synthesized a series of novel 3-aryl-1-(4-tert-butylbenzyl)-1H-pyrazole-5-carbohydrazide hydrazone derivatives and investigated their effects on A549 cell growth, the compound (E)-1-(4-tert-butylbenzyl)-NO-(1-(5-chloro-2-hydroxyphenylethylidene)-3-(4-chlorophenyl)-1H-pyrazole-5-carbohydrazide
(3e) possessed the highest growth inhibitory effect and induced apoptosis of A549 lung cancer cells [Figure 57]. | Figure 57: 3-aryl-1-(4- tert-butylbenzyl)-1H-pyrazole-5-carbohydrazide hydrazone derivatives
Click here to view |
Bruno et al.,[60] have reported the synthesis and the chemotaxis inhibitory activity of a number of 1H pyrazole-4-carboxylic acid ethyl esters. Few compounds have been reported as potent inhibitors of IL-8- and N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLPOMe) - stimulated Olga neutrophil chemotaxis. Most active compound (2e) in the fMLP-OMe induced chemotaxis test showed IC50 0.19–2 nM against dexamethasone as the standard compound [Figure 58].
Xiaet al.,[61] have synthesized a series of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide derivatives. Nine compounds of the series are reported to inhibit the growth of A549 cells and induced the cell apoptosis. Compounds with logP values in the range of 3.12–4.94 have been found to show more inhibiting effect on the growth of A549 cells. Compound 4b was found to be most potent [Figure 59]. | Figure 59: Novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide derivatives
Click here to view |
| Conclusion | | |
Literature survey shows that pyrazole derivatives are found to be pharmacologically more potent and hence their design and synthesis are the potential area of research. This has been noticed so far, that modification on pyrazole moiety displayed valuable biological activities. It will be interesting to observe that these modifications can be utilized as potent therapeutic agents in future. The biological profiles of these new generations of pyrazole would represent a fruitful matrix for the further development of better medicinal agents. Recent observations suggest that substituted pyrazole and heterocycles, which are the structural isosters of nucleotides owing fused heterocyclic nuclei in their structures that allow them to interact easily with the biopolymers, possess potential activity with lower toxicities in the chemotherapeutic approach in humans. For now, researchers have been attracted to designing more potent pyrazole derivatives having a wide diversity of biological activity.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21], [Figure 22], [Figure 23], [Figure 24], [Figure 25], [Figure 26], [Figure 27], [Figure 28], [Figure 29], [Figure 30], [Figure 31], [Figure 32], [Figure 33], [Figure 34], [Figure 35], [Figure 36], [Figure 37], [Figure 38], [Figure 39], [Figure 40], [Figure 41], [Figure 42], [Figure 43], [Figure 44], [Figure 45], [Figure 46], [Figure 47], [Figure 48], [Figure 49], [Figure 50], [Figure 51], [Figure 52], [Figure 53], [Figure 54], [Figure 55, [Figure 56], [Figure 57], [Figure 58], [Figure 59]
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| Gabriel C. Santos, Inaiá O. Rocha, Felipe S. Stefanello, João P. P. Copetti, Isadora Tisoco, Marcos A. P. Martins, Nilo Zanatta, Clarissa P. Frizzo, Bernardo A. Iglesias, Helio G. Bonacorso | | Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2021; : 120768 | | [Pubmed] | [DOI] | | | 26 |
Pd-catalyzed post-Ugi intramolecular cyclization to the synthesis of isoquinolone-pyrazole hybrid pharmacophores & discover their antimicrobial and DFT studies |
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| Keyur M. Pandya, Satyanarayana Battula, Parth J. Naik | | Tetrahedron Letters. 2021; 81: 153353 | | [Pubmed] | [DOI] | | | 27 |
New 1,2,3-Triazole-Appended Bis-pyrazoles: Synthesis, Bioevaluation, and Molecular Docking |
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| Ashruba B. Danne, Mukund V. Deshpande, Jaiprakash N. Sangshetti, Vijay M. Khedkar, Bapurao B. Shingate | | ACS Omega. 2021; 6(38): 24879 | | [Pubmed] | [DOI] | | | 28 |
Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids |
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| Nisheeth C. Desai, Kandarp Bhatt, Jahnvi Monapara, Unnat Pandit, Vijay M. Khedkar | | ACS Omega. 2021; 6(42): 28270 | | [Pubmed] | [DOI] | | | 29 |
Xanthohumol Pyrazole Derivative Improves Diet-Induced Obesity and Induces Energy Expenditure in High-Fat Diet-Fed Mice |
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| Ines L. Paraiso, Luce M. Mattio, Armando Alcázar Magaña, Jaewoo Choi, Layhna S. Plagmann, Margaret A. Redick, Cristobal L. Miranda, Claudia S. Maier, Sabrina Dallavalle, Chrissa Kioussi, Paul R. Blakemore, Jan F. Stevens | | ACS Pharmacology & Translational Science. 2021; | | [Pubmed] | [DOI] | | | 30 |
Rational Design, Synthesis and SAR Study of Novel Warfarin Analogous Of 4-Hydroxy Coumarin-Beta-Aryl Propanoic Acid Derivatives as Potent Anti-Inflammatory Agents. |
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| Varsha Pawar, Lokesh A. Shastri, Parashuram Gudimani, Shrinivas Joshi, Vijay M. Kumbar, Vinay Sunagar | | Journal of Molecular Structure. 2021; : 132300 | | [Pubmed] | [DOI] | | | 31 |
Design, synthesis, antibacterial evaluation and molecular docking studies of novel pyrazole/1,2,4-oxadiazole conjugate ester derivatives |
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| Navaneetha Depa, Harikrishna Erothu | | Medicinal Chemistry Research. 2021; 30(5): 1087 | | [Pubmed] | [DOI] | | | 32 |
Design, synthesis, in vitro determination and molecular docking studies of 4-(1-(tert-butyl)-3-phenyl-1H-pyrazol-4-yl) pyridine derivatives with terminal sulfonamide derivatives in LPS-induced RAW264.7 macrophage cells |
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| Karim I. Mersal, Mohammed S. Abdel-Maksoud, Eslam M. H. Ali, Usama M. Ammar, Seyed-Omar Zaraei, Jae-Min Kim, Su-Yeon Kim, Kyung-Tae Lee, Kwan Hyi Lee, Si-Won Kim, Hyun-Mee Park, Mi-Jung Ji, Chang-Hyun Oh | | Medicinal Chemistry Research. 2021; 30(10): 1925 | | [Pubmed] | [DOI] | | | 33 |
Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development |
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Ruthenium(II)-Catalyzed Direct
Ortho
Functionalization of 1-Arylpyrazoles with Maleimides: A Condition Controlled Installation of Succinimides and Maleimides on Arenes
|
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| Sagar D. Nale, Raju S. Thombal, Yong Rok Lee | | Asian Journal of Organic Chemistry. 2021; 10(9): 2374 | | [Pubmed] | [DOI] | | | 35 |
Iridium-Catalyzed Regio- and Enantioselective Borylation of Unbiased Methylene C(sp
3
)-H Bonds at the Position ß to a Nitrogen Center
|
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| Rongrong Du, Luhua Liu, Senmiao Xu | | Angewandte Chemie. 2021; 133(11): 5907 | | [Pubmed] | [DOI] | | | 36 |
Iridium-Catalyzed Regio- and Enantioselective Borylation of Unbiased Methylene C(sp
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| Rongrong Du, Luhua Liu, Senmiao Xu | | Angewandte Chemie International Edition. 2021; 60(11): 5843 | | [Pubmed] | [DOI] | | | 37 |
Design and synthesis of ferrocene-tethered pyrazolines and pyrazoles: Photophysical studies, protein-binding behavior with bovine serum albumin, and antiproliferative activity against MDA-MB-231 triple negative breast cancer cells |
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| Koena Ghosh, Nipa Nayek, Subhomoy Das, Nabendu Biswas, Samraj Sinha | | Applied Organometallic Chemistry. 2021; 35(7) | | [Pubmed] | [DOI] | | | 38 |
In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids |
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| Siti Munirah Mohd Faudzi, S. Wei Leong, Faruk A. Auwal, Faridah Abas, Lam K. Wai, Syahida Ahmad, Chau L. Tham, Khozirah Shaari, Nordin H. Lajis, Bohari M. Yamin | | Archiv der Pharmazie. 2021; 354(1): 2000161 | | [Pubmed] | [DOI] | | | 39 |
The inhibitory potency of isoxazole-curcumin analogue for the management of breast cancer: A comparative in vitro and molecular modeling investigation |
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Synthesis and biological evaluation of 3,5-substituted pyrazoles as possible antibacterial agents |
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| Matthew Payne, Amy L. Bottomley, Anthony Och, Anjar P. Asmara, Elizabeth J. Harry, Alison T. Ung | | Bioorganic & Medicinal Chemistry. 2021; 48: 116401 | | [Pubmed] | [DOI] | | | 41 |
Targeting NF-?B mediated cell signaling pathway and inflammatory mediators by 1,2-diazole in A549 cells in vitro |
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| Venugopal Vinod Prabhu, Perumal Elangovan, Sivasithambaram Niranjali Devaraj, Kunnathur Murugesan Sakthivel | | Biotechnology Reports. 2021; 29: e00594 | | [Pubmed] | [DOI] | | | 42 |
An expeditious one pot green synthesis of novel bioactive 1, 4-dihydropyridine derivatives at ambient temperature and molecular modelling |
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| Kailas A. More, Nilesh V. Gandhare, Parvez S. Ali, Naziyanaz B. Pathan, Khalid M. Al-Mousa | | Current Research in Green and Sustainable Chemistry. 2021; 4: 100108 | | [Pubmed] | [DOI] | | | 43 |
Antibacterial and antitumoral properties of 1,2,3-triazolo fused triterpenes and their mechanism of inhibiting the proliferation of HL-60 cells |
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| Rui Wang, Yang Li, Haibo Hu, Leentje Persoons, Dirk Daelemans, Steven De Jonghe, Walter Luyten, Besir Krasniqi, Wim Dehaen | | European Journal of Medicinal Chemistry. 2021; 224: 113727 | | [Pubmed] | [DOI] | | | 44 |
Cu(II) and Ag(I) complexes of the pyrazole-derived diorganoselenide (pzCH2CH2)2Se. Synthesis, solid state structure and solution behavior |
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| Roxana A. Popa, Vito Lippolis, Anca Silvestru | | Inorganica Chimica Acta. 2021; 520: 120272 | | [Pubmed] | [DOI] | | | 45 |
Synthesis of functionalized fluoroalkyl pyrimidines and pyrazoles from fluoroalkyl enones |
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| Elena N. Shaitanova, Olga A. Balabon, Antonina N. Rybakova, Tatyana S. Khlebnicova, Fedor A. Lakhvich, Igor I. Gerus | | Journal of Fluorine Chemistry. 2021; 252: 109905 | | [Pubmed] | [DOI] | | | 46 |
Correlation between corrosion inhibition efficiency in sulfuric acid medium and the molecular structures of two newly eco-friendly pyrazole derivatives on iron oxide surface |
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| N. Mechbal, M.E. Belghiti, N. Benzbiria, Chin-Hung Lai, Y. Kaddouri, Y. Karzazi, R. Touzani, M. Zertoubi | | Journal of Molecular Liquids. 2021; 331: 115656 | | [Pubmed] | [DOI] | | | 47 |
Urea derivatives of piperazine doped with pyrazole-4-carboxylic acids: Synthesis and antimicrobial evaluation |
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| Harshita Phougat, Vandana Devi, Sanjay Rai, T. Shreedhar Reddy, Karan Singh | | Journal of Heterocyclic Chemistry. 2021; 58(10): 1992 | | [Pubmed] | [DOI] | | | 48 |
Crystal structure determination of N- and O-alkylated tautomers of 1-(2-pyridinyl)-5-hydroxypyrazole |
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| Venkata S. Sadu, Yoon Mi Choi, Koteswara R. Kamma, Chong-Hyeak Kim, Yun Soo Bae, Kee-In Lee | | Journal of Molecular Structure. 2020; 1215: 128272 | | [Pubmed] | [DOI] | | | 49 |
Kinetics modelling of acid hydrolysis of cassava (Manihot esculanta Cranz) peel and its hydrolysate chemical characterisation |
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| E.O. Ajala, M.A. Ajala, I.A. Tijani, A.A. Adebisi, I. Suru | | Journal of King Saud University - Science. 2020; 32(4): 2284 | | [Pubmed] | [DOI] | | | 50 |
Computer-aided discovery of bis-indole derivatives as multi-target drugs against cancer and bacterial infections: DFT, docking, virtual screening, and molecular dynamics studies |
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| Parth Sarthi Sen Gupta, Haamid Rasool Bhat, Satyaranjan Biswal, Malay Kumar Rana | | Journal of Molecular Liquids. 2020; 320: 114375 | | [Pubmed] | [DOI] | | | 51 |
Recent advancement in the discovery and development of anti-epileptic biomolecules: An insight into structure activity relationship and Docking |
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| Mukund Jha, Ozair Alam, Mohd. Javed Naim, Vrinda Sharma, Parth Bhatia, Aadil Ahmad Sheikh, Farah Nawaz, Perwaiz Alam, Ajay Manaithiya, Vivek Kumar, Shagufi Nazar, Nadeem Siddiqui | | European Journal of Pharmaceutical Sciences. 2020; 153: 105494 | | [Pubmed] | [DOI] | | | 52 |
p-TSA.H2O mediated one-pot, multi-component synthesis of isatin derived imidazoles as dual-purpose drugs against inflammation and cancer |
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| M. Rajesh Kumar, V. Violet Dhayabaran, N. Sudhapriya, A. Manikandan, Daniel A. Gideon, S. Annapoorani | | Bioorganic Chemistry. 2020; 102: 104046 | | [Pubmed] | [DOI] | | | 53 |
2,4-Diketo esters: Crucial intermediates for drug discovery |
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| Nenad Joksimovic, Nenad Jankovic, Goran Davidovic, Zorica Bugarcic | | Bioorganic Chemistry. 2020; 105: 104343 | | [Pubmed] | [DOI] | | | 54 |
Copper-Catalyzed Regio- and Stereoselective 1,6-Conjugate Addition of Aza-Heterocycles to 1-Sulfonyl-1,3-dienes |
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| Subin Park, Hanseul Lee, Yunmi Lee | | Advanced Synthesis & Catalysis. 2020; 362(3): 572 | | [Pubmed] | [DOI] | | | 55 |
Transition-Metal-Free C-S Bond Forming Strategy towards Synthesis of Highly Diverse Pyrazole Tethered Benzothiazoles: Investigation of their Photophysical Properties |
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| Shubham Sharma, Chandi C. Malakar, Virender Singh | | Asian Journal of Organic Chemistry. 2020; 9(11): 1857 | | [Pubmed] | [DOI] | | | 56 |
Synthesis of pyrazolopyrimidines in mild conditions by gold nanoparticles supported on magnetic ionic gelation in aqueous solution |
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| Lanlan Yu, Shilong Xing, Kai Zheng, Seyed Mohsen Sadeghzadeh | | Applied Organometallic Chemistry. 2020; 34(7) | | [Pubmed] | [DOI] | | | 57 |
Nucleophilic Aromatic Substitution of Unactivated Fluoroarenes Enabled by Organic Photoredox Catalysis |
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| Vincent A. Pistritto, Megan E. Schutzbach-Horton, David A. Nicewicz | | Journal of the American Chemical Society. 2020; 142(40): 17187 | | [Pubmed] | [DOI] | | | 58 |
Pyrazole ligands and their monometallic and bimetallic complexes: synthesis, characterization, and application as novel corrosion inhibitors |
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| Asad Masoumi, Moayad Hossaini Sadr, Behzad Soltani | | Journal of Adhesion Science and Technology. 2020; 34(23): 2569 | | [Pubmed] | [DOI] | | | 59 |
Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico
Molecular Docking and ADME Prediction of 4-Chlorophenyl
Furfuran Derivatives bearing Pyrazole Moieties |
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| Manju Mathew, Raja Chinnamanayakar, Ezhilarasi Muthuvel Ramanathan | | Asian Journal of Chemistry. 2020; 32(6): 1482 | | [Pubmed] | [DOI] | | | 60 |
Highly Efficient Synthesis of New 3,5-Substituted (Isoxazolines) and 2,3,5-Trisubstituted (Pyrazolines) Mediated by Chloramin-T and Their Evaluation of Antioxidant and Antibacterial Activities |
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| Ebraheem Abdu Musad, Abdullah Mohammed Al Dawsari, Zaki Eldin Ali Abdalla, Kakul Husain, Razaz Saeed Saeed Al Sharabi, K. M. Lokanatha Rai | | Russian Journal of Bioorganic Chemistry. 2020; 46(5): 814 | | [Pubmed] | [DOI] | | | 61 |
Synthetic Methods and Antimicrobial Perspective of Pyrazole Derivatives: An Insight |
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| Harish Kumar, Kushal Kumar Bansal, Anju Goyal | | Anti-Infective Agents. 2020; 18(3): 207 | | [Pubmed] | [DOI] | | | 62 |
Nanocrystalline ZnO: A Competent and Reusable Catalyst for the Preparation of Pharmacology Relevant Heterocycles in the Aqueous Medium |
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| Moumita Saha, Asish R. Das | | Current Green Chemistry. 2020; 7(1): 53 | | [Pubmed] | [DOI] | | | 63 |
NSC 18725, a Pyrazole Derivative Inhibits Growth of Intracellular Mycobacterium tuberculosis by Induction of Autophagy |
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| Garima Arora, Gagandeep, Assirbad Behura, Tannu Priya Gosain, Ravi P. Shaliwal, Saqib Kidwai, Padam Singh, Shamseer Kulangara Kandi, Rohan Dhiman, Diwan S. Rawat, Ramandeep Singh | | Frontiers in Microbiology. 2020; 10 | | [Pubmed] | [DOI] | | | 64 |
Crystal structure of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate, C7H7F3N2O2 |
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| Željko. K. Jacimovic, Sladjana B. Novakovic, Goran A. Bogdanovic, Milica Kosovic, Eugen Libowitzky, Gerald Giester | | Zeitschrift für Kristallographie - New Crystal Structures. 2020; 235(5): 1189 | | [Pubmed] | [DOI] | | | 65 |
Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine As A Cannabinoid Receptor 1 Agonist |
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| Silvana Russo, Walter Filgueira de Azevedo | | Current Medicinal Chemistry. 2020; 27(28): 4741 | | [Pubmed] | [DOI] | | | 66 |
Microwave Assisted Reactions of Azaheterocycles Formedicinal Chemistry Applications |
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| Dorina Amariucai-Mantu, Violeta Mangalagiu, Ramona Danac, Ionel I. Mangalagiu | | Molecules. 2020; 25(3): 716 | | [Pubmed] | [DOI] | | | 67 |
Synthesis, Antimicrobial Activity and Molecular Docking of Pyrazole Bearing the Benzodiazepine Moiety |
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| Nisheeth. C. Desai, Surbhi B. Joshi, Vijay M. Khedkar | | Analytical Chemistry Letters. 2020; 10(3): 307 | | [Pubmed] | [DOI] | | | 68 |
Synthesis and crystal structure of 2-((1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)methylene)-2,3-dihydro-1H-inden-1-one, C23H16N2OS |
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| Alaa Alqahtani, Bakr F. Abdel-Wahab, Amany S. Hegazy, Benson M. Kariuki, Gamal A. El-Hiti | | Zeitschrift für Kristallographie - New Crystal Structures. 2019; 234(5): 969 | | [Pubmed] | [DOI] | | | 69 |
The crystal structure of N-(7-(4-fluorobenzylidene)-3-(4-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-indazole-2-carbonothioyl)benzamide, C28H23F2N3OS |
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| Mohammad Hayal Alotaibi, Bakr F. Abdel-Wahab, Obaid Fahad Aldosari, Amany S. Hegazy, Benson M. Kariuki, Gamal A. El-Hiti | | Zeitschrift für Kristallographie - New Crystal Structures. 2019; 234(5): 1083 | | [Pubmed] | [DOI] | | | 70 |
Ligand-Dependent Site-Selective Suzuki Cross-Coupling of 4-Bromopyrazol-5-yl Triflates |
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| Ryo Sakakibara, Kennosuke Itoh, Hideaki Fujii | | The Journal of Organic Chemistry. 2019; 84(18): 11474 | | [Pubmed] | [DOI] | | | 71 |
Copper-Catalyzed Aminoboration from Hydrazones To Generate Borylated Pyrazoles |
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| Kim N. Tu, Scott Kim, Suzanne A. Blum | | Organic Letters. 2019; 21(5): 1283 | | [Pubmed] | [DOI] | | | 72 |
DPD-Inspired Discovery of Novel LsrK Kinase Inhibitors: An Opportunity To Fight Antimicrobial Resistance |
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| Silvia Stotani, Viviana Gatta, Prasanthi Medarametla, Mohan Padmanaban, Anna Karawajczyk, Fabrizio Giordanetto, Päivi Tammela, Tuomo Laitinen, Antti Poso, Dimitros Tzalis, Simona Collina | | Journal of Medicinal Chemistry. 2019; 62(5): 2720 | | [Pubmed] | [DOI] | | | 73 |
Regioselective Thermal [3+2]-Dipolar Cycloadditions of a-Diazoacetates with
a
-Sulfenyl/Sulfinyl/Sulfonyl-
ß
-Chloroacrylamide Derivatives to Form Densely Functionalised Pyrazoles
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| Aaran J. Flynn, Alan Ford, U. B. Rao Khandavilli, Simon E. Lawrence, Anita R. Maguire | | European Journal of Organic Chemistry. 2019; 2019(31-32): 5368 | | [Pubmed] | [DOI] | | | 74 |
Oxidation of imidazole- and pyrazole-derived aldehydes by plant aldehyde dehydrogenases from the family 2 and 10 |
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| Jan Frömmel, Radka Koncitíková, David Kopecný, Miroslav Soural, Marek Šebela | | Chemico-Biological Interactions. 2019; 304: 194 | | [Pubmed] | [DOI] | | | 75 |
Selective, Ambient-Temperature C-4 Deuteration of Pyrazole Derivatives by D2O |
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| Basil M. Ahmed, Gellert Mezei | | The Journal of Organic Chemistry. 2018; 83(3): 1649 | | [Pubmed] | [DOI] | | | 76 |
Discovery of Novel Pyrazole-Based Selective Aldosterone Synthase (CYP11B2) Inhibitors: A New Template to Coordinate the Heme-Iron Motif of CYP11B2 |
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| Ryo Sakakibara, Wataru Sasaki, Yuichi Onda, Minami Yamaguchi, Hideki Ushirogochi, Yuki Hiraga, Kanako Sato, Masashi Nishio, Yasuhiro Egi, Kei Takedomi, Hidetoshi Shimizu, Tomoko Ohbora, Fumihiko Akahoshi | | Journal of Medicinal Chemistry. 2018; 61(13): 5594 | | [Pubmed] | [DOI] | | | 77 |
Recent progress on anti-cancer of amide appended heterocyclic and its possible therapeutic applications. A review drug progress for cancer therapeutics. |
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| YASSER HUSSEIN EISSA MOHAMMED, SHAUKATH ARA KHANUM | | International Journal of pharma and Bio Sciences. 2018; 9(2) | | [Pubmed] | [DOI] | | | 78 |
Copper-catalyzed methylation of 1,3-diketones with tert -butyl peroxybenzoate |
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Chalcone: A valuable scaffold upgrading by green methods |
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| Gonçalo P. Rosa,Ana M. L. Seca,Maria do Carmo Barreto,Diana Cláudia Gouveia Alves Pinto | | ACS Sustainable Chemistry & Engineering. 2017; | | [Pubmed] | [DOI] | | | 80 |
Crystal structure of (E)-5-((4-chlorophenyl)diazenyl)-2-(5-(4-fluorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazole, C23H17ClFN5S2 |
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| Gamal A. El-Hiti, Bakr F. Abdel-Wahab, Mohammed Baashen, Amany S. Hegazy, Benson M. Kariuki | | Zeitschrift für Kristallographie - New Crystal Structures. 2017; 232(1): 157 | | [Pubmed] | [DOI] | | | 81 |
Anticancer activity profiling of parthenolide analogs generated via P450-mediated chemoenzymatic synthesis |
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| Hanan Alwaseem,Benjamin J. Frisch,Rudi Fasan | | Bioorganic & Medicinal Chemistry. 2017; | | [Pubmed] | [DOI] | | | 82 |
Synthesis, Antimicrobial and Antioxidant Activity of Pyrazole Based Sulfonamide Derivatives |
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| Jagdish R. Badgujar,Dhananjay H. More,Jyotsna S. Meshram | | Indian Journal of Microbiology. 2017; | | [Pubmed] | [DOI] | | | 83 |
Experimental and theoretical studies of a pyrazole-thiazolidin-2,4-di-one hybrid |
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Facile one-pot multicomponent synthesis of 1H-pyrazolo[3,4-b]quinolines using L-proline as a catalyst |
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| Hemant Hegde,Nitinkumar S. Shetty | | Chemistry of Heterocyclic Compounds. 2017; | | [Pubmed] | [DOI] | | | 85 |
Synthesis of Functionalized Pyrazoles via
1,3-Dipolar Cycloaddition of a
-Diazo-ß
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Analgesic, anti-inflammatory, and antimicrobial activities of novel isoxazole/pyrimidine/pyrazole substituted benzimidazole analogs |
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| Krishna Veni Chikkula,Raja Sundararajan | | Medicinal Chemistry Research. 2017; | | [Pubmed] | [DOI] | | | 87 |
Brønsted-acidic ionic liquid: green protocol for synthesis of novel tetrasubstituted imidazole derivatives under microwave irradiation via multicomponent strategy |
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Convergent synthesis and cytotoxicity of novel trifluoromethyl-substituted (1H-pyrazol-1-yl)(quinolin-4-yl) methanones |
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| Helio G. Bonacorso,Pablo A. Nogara,Fernanda D’A. Silva,Wilian C. Rosa,Carson W. Wiethan,Nilo Zanatta,Marcos A.P. Martins,João B.T. Rocha | | Journal of Fluorine Chemistry. 2016; 190: 31 | | [Pubmed] | [DOI] | | | 89 |
Synthesis, carbonic anhydrase I and II inhibition studies of the 1,3,5-trisubstituted-pyrazolines |
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| Halise Inci Gul,Ebru Mete,Parham Taslimi,Ilhami Gulcin,Claudiu T. Supuran | | Journal of Enzyme Inhibition and Medicinal Chemistry. 2016; : 1 | | [Pubmed] | [DOI] | |
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