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Review
. 2018 Jan 12;23(1):134.
doi: 10.3390/molecules23010134.

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Khalid Karrouchi  1   2   3 , Smaail Radi  4 , Youssef Ramli  5 , Jamal Taoufik  6 , Yahia N Mabkhot  7 , Faiz A Al-Aizari  8 , M'hammed Ansar  9
Affiliations
Review

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Khalid Karrouchi et al. Molecules. .

Abstract

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

Keywords: biological activities; pyrazole derivatives; synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pharmaceutical drugs containing pyrazole unit.
Figure 2
Figure 2
Structure of pyrazole.
Figure 3
Figure 3
Examples of α,β-unsaturated carbonyl compounds.
Scheme 1
Scheme 1
Synthesis of polysubstituted pyrazoles form 1,3-dicarbonyl compounds.
Scheme 2
Scheme 2
Synthesis of 1,3,5-substituted pyrazoles from ethyl acetoacetate.
Scheme 3
Scheme 3
Synthesis of 1,3,4,5-substituted pyrazoles from 2-(trifluoromethyl)-1,3-diketone.
Scheme 4
Scheme 4
Synthesis of pyrazoles from 1,3-diketones and arylhydrazines.
Scheme 5
Scheme 5
Synthesis of pyrazoles from acetylenic ketones.
Scheme 6
Scheme 6
Synthesis of pyrazoles from diacetylene ketones.
Scheme 7
Scheme 7
Synthesis of 3-trifluoromethylpyrazoles via cyclization of acetylenic ketones.
Scheme 8
Scheme 8
Synthesis of 3,5-diarylpyrazoles from acetylenic ketones and hydrazines derivatives.
Scheme 9
Scheme 9
Synthesis of pyrazoles by cyclocondensation reaction of α,β-ethylenic ketone.
Scheme 10
Scheme 10
Synthesis of pyrazoles from α,β-ethylenic ketone.
Scheme 11
Scheme 11
Synthesis of 3,5-diaryl-1H-pyrazoles from β-arylchalcones.
Scheme 12
Scheme 12
Synthesis of 4-alkyl-1,3,5-triarylpyrazoles from α,β-ethylenic ketones.
Scheme 13
Scheme 13
Synthesis of pyrazoles by cyclocondensation reaction of the α,β-ethylenic ketone.
Scheme 14
Scheme 14
Synthesis of pyrazoles via cyclocondensation of α,β-ethylenic ketones having a leaving group.
Scheme 15
Scheme 15
Synthesis of pyrazoles from α-oxoketene O,N-acetals and enaminodicketones.
Scheme 16
Scheme 16
Synthesis of pyrazoles starting from α-benzotriazolylenones.
Scheme 17
Scheme 17
Synthesis of pyrazoles from β-aminoenones.
Scheme 18
Scheme 18
Synthesis of pyrazoles from β-aminoenones.
Scheme 19
Scheme 19
Synthesis of pyrazoles by 1,3-dipolar cycloaddition of ethyl α-diazoacetate.
Scheme 20
Scheme 20
Synthesis of pyrazole-5-carboxylates using 1,3-dipolar cycloaddition of ethyl diazoacetate and α-methylene carbonyl.
Scheme 21
Scheme 21
Synthesis of pyrazoles using 1,3-dipolar cycloaddition of α-diazoarylacetacetates.
Scheme 22
Scheme 22
Synthesis of 3-acylpyrazoles using 1,3-dipolar cycloaddition of diazocarbonyl and acetylides.
Scheme 23
Scheme 23
Synthesis of pyrazoles by cycloaddition reaction of sydnones and alkyne.
Scheme 24
Scheme 24
Synthesis of pyrazoles by 1,3-dipolar cycloaddition of arylsydnones and chalcone.
Scheme 25
Scheme 25
Synthesis of pyrazole by 1,3-dipolar cycloaddition of diphenylnitrilimine and alkene.
Scheme 26
Scheme 26
Synthesis of pyrazole via 1,3-dipolar cycloaddition reaction of nitrilimine and vinyl.
Scheme 27
Scheme 27
Synthesis of pyrazole from α,β-unsaturated carbonyl and hydrazine.
Scheme 28
Scheme 28
Synthesis of pyrazole via cyclocondensation reaction of 1,3-dicarbonyl and arylhydrazine.
Scheme 29
Scheme 29
Synthesis of pyrazoles by one-pot reaction of aryl iodides, acetylenic acids and methylhydrazine.
Scheme 30
Scheme 30
Synthesis of 3,5-diphenylpyrazoles via cuprocatalyzed coupling between alkyne and oxime.
Scheme 31
Scheme 31
Synthesis of pyrazoles by one-pot cyclization of hydrazone with diethyl dioxalate.
Scheme 32
Scheme 32
Synthesis of carboxaldehyde pyrazoles by Vilsmeier-Haack reaction.
Scheme 33
Scheme 33
Synthesis of 1,3,4,5-Substituted pyrazole derivatives.
Scheme 34
Scheme 34
Synthesis of pyrazoles by 1,3-dipolar cycloaddition of diazo derivatives.
Scheme 35
Scheme 35
Synthesis of pyrazoles from pyranones.
Scheme 36
Scheme 36
Synthesis of pyrazoles by reaction of pyranones derivatives with hydrazine.
Scheme 37
Scheme 37
Synthesis of pyrazoles from furandiones.
Scheme 38
Scheme 38
Synthesis of pyrazoles from pyrimidines and pyrimidones.
Scheme 39
Scheme 39
Synthesis of pyrazoles from oxazoles.
Scheme 40
Scheme 40
Synthesis of pyrazoles from oxazoles.
Scheme 41
Scheme 41
Synthesis of pyrazoles from tetrazoles.
Scheme 42
Scheme 42
Synthesis of pyrazoles from triazines.
Scheme 43
Scheme 43
Synthesis of pyrazoles from 1,5-Benzodiazepin-2-one.
Scheme 44
Scheme 44
Synthesis of pyrazoles from (Z)-3-Acetyl-2-methyl-2,3-dihydro-1,4-benzodioxin-2-ol.
Scheme 45
Scheme 45
Synthesis of pyrazoles from ethyl-1-amino-6,7-difluorooxoquinolin-4-one-3-carboxylate.
Scheme 46
Scheme 46
Synthesis of pyrazoles from 3-methyl-6H-1,3,4-thiadiazine.
Scheme 47
Scheme 47
Synthesis of pyrazoles from nitropyrimidine.
Scheme 48
Scheme 48
Synthesis of pyrazoles by condensation of thietanone and 1,2,4,5-tetrazines.
Figure 4
Figure 4
Structures of some pyrazole derivatives as antimicrobial compounds.
Figure 5
Figure 5
Structures of some pyrazole derivatives with antibacterial activity.
Figure 6
Figure 6
Pyrazole derivatives with antimicrobial activity.
Figure 7
Figure 7
Pyrazole derivatives showing antimicrobial activity.
Figure 8
Figure 8
Pyrazole derivatives with antimicrobial activity.
Figure 9
Figure 9
Pyrazole derivatives with antimicrobial activity.
Figure 10
Figure 10
Pyrazole derivatives with antimicrobial activity.
Figure 11
Figure 11
Pyrazole derivatives with antimicrobial activity.
Figure 12
Figure 12
Structures of pyrazole derivatives with anticancer activity.
Figure 13
Figure 13
Pyrazole derivatives showing anticancer activity.
Figure 14
Figure 14
Pyrazole derivatives with anticancer activity.
Figure 15
Figure 15
Pyrazole derivatives with anticancer activity.
Figure 16
Figure 16
Pyrazole derivatives with anticancer activity.
Figure 17
Figure 17
Pyrazole derivatives with anticancer activity.
Figure 18
Figure 18
Pyrazole derivatives with anticancer activity.
Figure 19
Figure 19
Pyrazole derivatives with anticancer activity.
Figure 20
Figure 20
Some structures of pyrazoles with anticancer activity.
Figure 21
Figure 21
Pyrazole derivatives with anticancer activity.
Figure 22
Figure 22
Pyrazole derivatives with anticancer activity.
Figure 23
Figure 23
Pyrazole derivatives with anti-inflammatory activity.
Figure 24
Figure 24
Pyrazole derivatives with anti-inflammatory and analgesic activities.
Figure 25
Figure 25
Pyrazole derivatives with anti-inflammatory and analgesic activities.
Figure 26
Figure 26
Pyrazole derivatives with anti-inflammatory and analgesic activities.
Figure 27
Figure 27
Pyrazole derivatives with anti-inflammatory activity.
Figure 28
Figure 28
Pyrazole derivatives with anti-inflammatory activity.
Figure 29
Figure 29
Pyrazole derivatives with anti-tubercular activity.
Figure 30
Figure 30
Pyrazole derivatives with anti-tubercular activity.
Figure 31
Figure 31
Pyrazole derivatives with anti-tubercular activity.
Figure 32
Figure 32
Pyrazole derivatives with anti-tubercular activity.
Figure 33
Figure 33
Pyrazole derivatives with anti-tubercular activity.
Figure 34
Figure 34
Pyrazole derivatives with anti-tubercular activity.
Figure 35
Figure 35
Pyrazole derivatives with anti-viral activity.
Figure 36
Figure 36
Pyrazole derivatives with anti-viral activity.
Figure 37
Figure 37
Pyrazole derivatives with anti-viral activity.
Figure 38
Figure 38
Pyrazole derivatives with anti-viral activity.
Figure 39
Figure 39
Pyrazole derivatives with anti-viral activity.
Figure 40
Figure 40
Pyrazole derivatives with anti-azheimer activity.
Figure 41
Figure 41
Pyrazole derivatives as anti-azheimer’s compounds.
Figure 42
Figure 42
Pyrazole derivatives with anti-diabetic activity.
Figure 43
Figure 43
Pyrazole derivatives with anti-diabetic activity.
Figure 44
Figure 44
Pyrazole derivatives with anti-diabetic activity.
Figure 45
Figure 45
Pyrazole derivatives with anti-diabetic activity.
Figure 46
Figure 46
Pyrazole derivatives with anti-leishmanial activity.
Figure 47
Figure 47
Pyrazole derivatives with anti-malarial activity.
Figure 48
Figure 48
Pyrazole derivatives with anti-parkinson activity.
Figure 49
Figure 49
Agrochemical molecules containning pyrazole scaffold.
Figure 50
Figure 50
Pyrazole derivatives with insecticidal and acaricidal activities.
Figure 51
Figure 51
Pyrazole derivatives with pesticidal activity.
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