Asian Journal of Biochemical and Pharmaceutical Research Recent Advances on the Synthesis of Pyrazole-Containing Compounds of Potent Biological Activities and Study Their Chemical Applications

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Asian Journal of Biochemical and Pharmaceutical Research Recent Advances
on the Synthesis of Pyrazole-Containing Compounds of Potent Biological
Activities and Study Their Chemical...
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Asian Journal of Biochemical and Pharmaceutical Research Issue 3 (Vol. 4) 2014 ISSN: 2231-2560
CODEN (USA): AJBPAD
Review Article
356
Asian Journal of Biochemical and Pharmaceutical Research
Recent Advances on the Synthesis of Pyrazole-Containing Compounds of Potent
Biological Activities and Study Their Chemical Applications
Taha M.A Eldebss
Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt
Received: 16 September 2014; Revised: 14 October 2014; Accepted: 19 November 2014
Abstract: Several pyrazoles with different substitutions at different position were synthesized starting from
pyrazole and its derivatives. The biological activities of newly synthesized compounds were tested and
evaluated in vivo and vitro for different types of diseases and exhibited good results, in addition to some
examples of some Pyrazoles Containing Compounds were established as drugs such as Celecoxib Lesopitron
Sulfaphenazole Rimonabant Tebufenpyrad Betazole Tepoxalin Pyriprole Deracoxib Mavacoxib.
Keywords: Pyrazole, Celecoxib, Lesopitron, Pyriprole, Yellow 2G, Fipronil RS.
INTRODUCTION:
Structurally unique and functionality-enriched heterocyclic systems are of great significance in
chemically and biologically related research areas.[ 2-112, 187-134] In particular, pyrazole and their
derivatives are an important classes of compounds and has been widely found in biologically active
molecules and drug candidates. Moreover, diversely functionalized pyrazole have also been identified
as versatile synthetic building blocks for the construction of complex molecules and natural products.
Therefore, great efforts have been done to their preparations and chemical application.
3 -Properties of pyrazole as in Fig.1
Fig.1
Pyrazole (Systematic or IUPAC name 1,2-Diazole) It is a heterocyclic organic compound
characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen centres with the
molecular formula C3H4N2 ; molar mass, 68.08 g mol−1; melting point, 66–70 °C, boiling point,

Asian Journal of Biochemical and Pharmaceutical Research Issue 3 (Vol. 4) 2014
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186–188 °C ; basicity (pKb), 2.5, . Pyrazoles are also the class of compounds that have the ring
C3N2 with adjacent nitrogen centres [1].
4- Chemical reactivity and application of pyrazoles
4-1) Methods of Synthesis of pyrazoles
4-1-1) Synthesis of unsubstitute Pyrazole
Pyrazole was synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent
dehydrogenation as in Scheme1 [113].
Scheme 1
4-1-2))Knorr pyrazole synthesis The Knorr pyrazole synthesis is an organic reaction used to convert a
hydrazine or its derivatives and a 1,3-dicarbonyl compound to a pyrazole using an acid catalyst via the
following mechanism as in Scheme 2 [114].
R1
O
R3
O
R2
H3O
R1
OH
R3
O
R2
RNHNH2
-H2O
R1
OH
R3
O
R2
RNHNH2
H2O
-H3O R1
OH
R3
O
R2
RNHNH
R1 R3
O
R2
RNHN
H3O
-H2O
R1 R3
OH
R2
RNHN
-H2O N
N
R3
OH
R1
R2
R
H
N
N
R3
R1
R2
Scheme :2
4-1-3) Substituted and unsubstituted pyrazoles are prepared by condensation of 1,3-diketones with
hydrazine. For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole as in Scheme 3
[115].
CH3C(O)CH2C(O)CH3 + N2H4 → (CH3)2C3HN2H + 2 H2O
Scheme 3
Also, pyrazole was synthesized from acetylene and diazomethane[116].

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4-2) Synthesis of substituted pyrazole
4-2-1)Synthesis of novel pyrazole-based heterocycles via a copper(II)-catalysed domino annulations
Pyrazole-based β-aminonitriles and β-amino-carbaldehydes as bifunctional building blocks are
introduced in a facile copper(II)-catalysed one-pot domino generation of multiple N-containing
heterobi- and tricycles. This streamlined synthetic approach permits easy access to novel pyrazole-
fused imidazo- and pyrimido[1,2-c]pyrimidinones and to pyrazolo[3,4-d]pyrimidinone species with
isolated yields up to 90%. The present study also reveals a unique amine–isocyanate coupling
promotion via copper(II)-based catalytic activation as in Scheme 4 [117].
Scheme 4
4-2-2) Heterocycle formation from 1,3-dinitroalkanes. A novel pyrazole synthesis: Combinatorial
Chemistry Review.Aliphatic nitro compounds have proved to be useful starting materials in organic
synthesis. When the nitro compounds are properly substituted they can cyclize, yielding heterocyclic
compounds. 1,3-Dinitroalkanes can be viewed as synthetic equivalents for 1,3-dicarbonyl compounds
through a Nef, or equivalent, reaction, and therefore could be ultimately converted into azole
heterocycles. Application of the Nef reaction under the usual conditions (NaOH; conc. H2SO4) to 1,3-
dinitroalknes gives only trace amounts of the anticipated dione, although the yields can be increased
(up to 40%) using a secondary amine as the base. We now find that 1,3-dinitroalkanes react with
hydrazines giving rise to pyrazoles as in Scheme 5 [118].
Scheme 5

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4-2-3) An efficient, general, one-pot, three-component procedure for the preparation of 3,5-
disubstituted 1H-pyrazoles includes condensation of substituted aromatic aldehydes and
tosylhydrazine followed by cycloaddition with terminal alkynes. The reaction tolerates various
functional groups and sterically hindered substrates to afford the desired pyrazoles in good yields as in
Scheme 6 [119].
Scheme 6
4-2-4) 1,3-Diketones, which were synthesized in situ from ketones and acid chlorides, were converted
into pyrazoles by the addition of hydrazine. This method allows a fast and general synthesis of
previously inaccessible pyrazoles and synthetically demanding pyrazole-containing fused rings as in
Scheme 7 [120].
Scheme 7
4-2-5) A highly regioselective synthesis of 1-aryl-3,4,5-substituted pyrazoles based on the
condensation of 1,3-diketones with arylhydrazines proceeds at room temperature in N,N-
dimethylacetamide and furnishes pyrazoles in good yields as in Scheme 8[121].
.
Scheme 8
4-2-6) Pyrazole or isoxazole derivatives are prepared by a palladium-catalyzed four-component
coupling of a terminal alkyne, hydrazine (hydroxylamine), carbon monoxide under ambient pressure,
and an aryl iodide as in Scheme 9[122].

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Scheme 9
4-2-7) Also, pyrazoles derivatives were obtained via reaction of aryl halides with 1,3-diones as in
Scheme 10[123].
Scheme 10
4-2-8) pyrazoles derivatives were obtained via one-pot, three-components synthesis as in Scheme
11[124].
Scheme 11
4-2-9) A regioselective synthesis of tri- or tetrasubstituted pyrazoles by the reaction of hydrazones
with nitroolefins mediated with strong bases such as t-BuOK exhibits a reversed, exclusive 1,3,4-
regioselectivity. Subsequent quenching with strong acids such as TFA is essential to achieve good
yields. A stepwise cycloaddition reaction mechanism is proposed as in Scheme 12[125].
Scheme 12
4-2-10) Two general protocols for the reaction of electron-deficient N-arylhydrazones with
nitroolefins allow a regioselective synthesis of 1,3,5-tri- and 1,3,4,5-tetrasubstituted pyrazoles. Studies
on the stereochemistry of the key pyrazolidine intermediate suggest a stepwise cycloaddition
mechanism as in Scheme 13[126].

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Scheme 13
4-2-11) A regioselective one-pot synthesis of substituted pyrazoles from N-monosubstituted
hydrazones and nitroolefins gives products in good yields. A key nitropyrazolidine intermediate is
characterized and a plausible mechanism is proposed as in Scheme 14[127].
Scheme 14
4-2-12) An unprecedented ruthenium(II)-catalyzed oxidative C-N coupling method enables a facile
intramolecular synthesis of various synthetically challenging tri- and tetrasubstituted pyrazoles in the
presence of oxygen as oxidant. The reaction demonstrates excellent reactivity, functional group
tolerance, and high yields as in Scheme 15[128].
Scheme 15
4-2-13) A general, highly flexible Cu-catalyzed domino C-N coupling/hydroamination reaction
constitutes a straightforward alternative to existing methodology for the preparation of pyrroles and
pyrazoles as in Scheme 16[129].
Scheme 16
4-2-14) Alumino-heteroles are obtained from simple precursors in a fully chemo- and regioselective
manner by a metalative cyclization. The carbon-aluminum bond is still able to react further with
several electrophiles, without the need of transmetalation providing a straightforward access to 3,4,5-
trisubstituted isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles as in Scheme 17[130].

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Scheme 17
4-2-15) Various 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles have been prepared in good yields from
the corresponding 2-alkyn-1-ones. The resulting dihydropyrazoles undergo dehydration and iodination
in the presence of ICl and Li2CO3 at room temperature to provide 1-acyl-4-iodo-1H-pyrazoles as in
Scheme 18[131].
Scheme 18
4-2-16) A tandem catalytic cross-coupling/electrocyclization allows the conversion of differentially
substituted acyclic and cyclic enol triflates and an elaborated set of diazoacetates to provide the
corresponding 3,4,5-trisubstituted pyrazoles with a high degree of structural complexity as in Scheme
19[132].
Scheme 19
4-2-17) A series of 4-substituted 1H-pyrazole-5-carboxylates was prepared from the
cyclocondensation reaction of unsymmetrical enaminodiketones with tert-butylhydrazine
hydrochloride or carboxymethylhydrazine. The compounds were obtained regiospecifically and in
very good yields as in Scheme 20[133].
Scheme 20

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4-2-18) An easy and efficient copper-catalyzed reaction for the synthesis of polysubstituted pyrazoles
from phenylhydrazones and dialkyl ethylenedicarboxylates tolerates a range of functionalities, and the
corresponding adducts can be obtained in moderate to good yields as in Scheme 21[134].
Scheme 21
4-2-19) The reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones
gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted
pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate as
in Scheme 22[135].
Scheme 22
4-2-20) In the presence of activated carbon, Hantzsch 1,4-dihydropyridines and 1,3,5-trisubstituted
pyrazolines were aromatized with molecular oxygen to the corresponding pyridines and pyrazoles in
excellent yields as in Scheme 23[136].
.
Scheme 23
4-2-21) CuI-catalyzed coupling of N-acyl-N′-substituted hydrazines with aryl iodides affords N-acyl-
N′,N′-disubstituted hydrazines regioselectively. N-Acyl-N′-substituted hydrazines can also react with
2-bromoarylcarbonylic compounds in the presence of 4-hydroxy-L-proline as ligand to provide 1-aryl-
1H-indazoles as in Scheme 24[137].

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Scheme 24
4-2-22) Various N-aryl-1H-indazoles and benzimidazoles were synthesized from common arylamino
oximes in good to excellent yields depending upon the base used in the reaction. Triethylamine
promoted the formation of benzimidazoles, whereas 2-aminopyridine promoted the formation of N-
arylindazoles as in Scheme 25[138].
Scheme 25
4-2-23) A rapid and efficient synthesis of 2H-indazoles, which involves a [3 + 2] dipolar
cycloaddition of arynes and sydnones, proceeds under mild reaction conditions in good to excellent
yields as in Scheme 26[139].
.
Scheme 26
4-2-24) The 1H-indazole skeleton can be constructed by a [3 + 2] annulation approach from arynes
and hydrazones. Under different reaction conditions, both N-tosylhydrazones and N-
aryl/alkylhydrazones can be used to afford various indazoles as in Scheme 27[140].

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.
Scheme 27
4-2-25) Readily available, stable, and inexpensive N-tosylhydrazones react with arynes under mild
reaction conditions to afford 3-substituted indazoles in good yields. The reaction involves a 1,3-dipolar
cycloaddition of in situ generated diazo compounds and arynes as in Scheme 28[141].
.
Scheme 28
4-2-26) The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in
the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide
range of potentially biologically and pharmaceutically interesting substituted indazoles in good to
excellent yields under mild reaction conditions as in Scheme 29[142].
.
Scheme 29
4-2-27) 2H-Indazoles are synthesized using a copper-catalyzed one-pot, three-component reaction of
2-bromobenzaldehydes, primary amines, and sodium azide. The catalyst plays the key role in the
formation of C-N and N-N bonds. This method has a broad substrate scope with a high tolerance for
various functional groups as in Scheme 30[143].
Scheme 30
4-2-28) A general two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles
involves a palladium-catalyzed arylation of benzophenone hydrazone followed by an acidic
deprotection/cyclization sequence. This procedure offers a general and efficient alternative to the
typical SNAr reaction of hydrazine with o-fluorobenzonitriles as in Scheme 31[144].

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Scheme 31
4-2-29) Compounds containing imine showed high insecticidal activity against cotton bollworm. The
compounds also had good activities against bean aphid and mosquito as in Scheme 32[145].
Scheme 32
4-2-30) One-pot three-components synthesis of benzochromeno-pyrazole derivatives as in Scheme
33[146].
Scheme 33
4-2-31) pyrazole carboxylate derivatives can be converted into pyrazolotriazolo, pyrazolo thiadiazolo,
pyrazolo oxiadiazolo and bipyrazolo derivatives as in Schemes 34, 35, 36, 37 and 38 [5].
Ph
N N
Ph
CN OC2H5
O
Ph
N
N
Ph
CN
H
N
N N
HS
NH2NH2 / R.T
S
NHNH2
H2N
KSCN
KOH
OR
Scheme 34

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Ph
N N
Ph
CN OC2H5
O
Ph
N
N
Ph
CN
N
N N
Y
NH2NH2 / R.T
S
NHNH2
H2N
/ KSCN
KOH
Or
Or PhCNS/KOH/NH2NH2
Or CS2/KOH/NH2NH2
X
X = H, NH2, Ph
Y = SH, SH, NH2NH2
Scheme 35
ٍ◌Scheme 36
PhNCS
Ph
N
N
Ph
CN
S
N N
PhHN
H2SO4
Ph
N
N
Ph
CN
HN
O
NH2
Ph
N
N
Ph
CN
O
N N
HS
CS2 / KOH
Reflux
Scheme 37
O
O
O
OEt
O
Ph
N
N
Ph
NC
O
N
N
Ph
N N
Ph
NC O
N
N
O
Ph
N
N
Ph
CN
HN
O
NH2
Scheme 38
Ph
N N
Ph
CN OC2H5
O
Ph
N
N
Ph
CN
H
N
N N
HS
NH2NH2 / R.T
S
NHNH2
H2N
KSCN
KOH
OR

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4-2-32) pyrazole enaminone derivatives can be converted into pyrazolo pyrazolopyradizine and
bipyrazolo derivatives as in Schemes 39, 40, 41[4].
Ph
N
N
NC
O
N
Dry benzene/
Et3N/
N
N
Ph
N
N
N
N
Ar
Ph
NC
X
NH2NH2
Ph
YCOC(Cl)NNHAr
Y
X
CH3, OMe
CH3, OH
Scheme 39
Ph
N
N
NC
O
N
Dry benzene/
Et3N/
N
N
Ph
Ph
NC
NH2NH2
Ph
PhNHCOC(Cl)NNHAr
O
N
N
NH
O
Ar
Ph
N
N
Ph
Ph
NC
O
N
N
Ph
Ph
PhC(Cl)NNHAr
Dry benzene/
Et3N/ NH2NH2
Scheme 40
Ph
N
N
Ph
NC
O Br
N NH
Ar
N
N
Ph
N
N
N
N
Ar
Ph
NC
NH
N
N CN
Ph Ph
Ph
N
N
NC
O
N
Dry benzene/
Et3N/ NH2NH2
Ph
Scheme 41
4-2-33) Enaminone reacts with hydrazines , hydroxylamine and guanidine to afford the novel
pyrazole, isoxazole and pyrimidine derivatives, respectively. It reacts also with aminopyrazole
derivatives to pyrazolo[1,5-a]pyrimidine derivatives. Reaction of the enaminone reacts with
benzoquinone and naphthoquinone led to the formation benzofuran derivatives, respectively. In

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addition, it reacts with hippuric acid to afford the corresponding pyrazolyl pyranone derivative as in
Scheme 42[147].
N
X
H2N NH2
NH
NH2X
, X= O,N ,NPh
N
N
H3C
Ph
O
NMe2
N
N
H3C
Ph
N
N
H3C
Ph
N
N
NH2
N
NH
NH2
N
N
N
R2
R1
R1
R2
N
N
H3C
Ph
O
O
O
O
N
N
H3C
Ph
O
OH
O
N
N
H3C
Ph
O
OH
O
COOH
HN
O
Ph O O
H
N O
Ph
N
N
H3C
Ph
Scheme 42
4-2-34) Enaminone undergoes regioselective 1,3-dipolar cycloaddition with nitrilimines and nitrile
oxides to afford the novel pyrazole and isoxazole derivatives, respectively. It reacts also with 1H-
benzimidazole-2-acetonitrile, 2-aminobenzimidazole and 3-amino-1,2,4-triazole to afford the novel
pyrido[1,2-a]benzimidazole, pyrimido[1,2-a]benzimidazole and the triazolo[1,5-a]pyrimidine
derivatives, respectively as in Scheme 43[148].

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N
N
CH3
Ph
N
N
CN
N N
CH3
Ph
N
N
N
N
N N
CH3
Ph
N
N
N
N
N
N N
CH3
Ph
N
N
CH3
Ar
N
N
CH3
Ph
O
H3C
R
O
N
Z
ArHN
Z = Cl, Br
R = CH
3, OEt
-HNMe2
N
H
N CN
N
H
N
NH2
N
N
NH
NH2
Scheme 43
4-2-35) simple, facile, efficient and three-components procedure for the synthesis Pyrazolo[3,4-
b]pyridines utilizing phenylsulphone synthon, under ultrasonic irradiation as in Scheme 44[149].
abs. ethanol /
p-TsOH
))) or Reflux
+
N
N
Ph
NH2
N
N N
Ph
Ar
Ph
R R
Ph
O
S
O O
Ph
Ar
Scheme 44
4-2-36)-J. K. Sneed et.al reported[ 150, 151] that 3, 5-Di (2-pyridyl) pyrazole 26 was first obtained in
the reaction of 1, 3-di (2-pyridyl) propane-1, 3-dione 25 with hydrazine hydrate. A series of mono- and
di (4-pyridyl)-substituted pyrazoles were synthesized using the same approach as in Scheme 45.
N
N
H
N
R
N
O
R
O
NH2NH2
Scheme 45
4-2-37)-J A. Silkhankova et.al reported [152, 153] a large volume of the research was done by the
authors who synthesized a series of symmetrical and unsymmetrical 3, 5-dipyridyl-substituted
pyrazoles as in Scheme 46.

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N
N
R3
R2
R1
O
R2
O
R3NHNH2 R1
Scheme 46
4-2-37)-A biologically active series of substituted pyrazoles were synthesized as in Fig.2 [154].
Fig.2
4-2-38)-4-iodopyrazoles was synthesized under microwave conditions as in Scheme 47[155].
N
N
H
N
N
H
microwave or
coventional heated
75-77%
I
Scheme 47
4-2-39)-N-Substituted benzoylpyrazoles as shown below as in Scheme 48[156].
R1
F3C
OH
O
EtOH / H+
N2H4 (aq.)
R1
F3C
NH-NH2
O
R1
F3C
N
O
N
H3C
CH3
O O
Scheme 48
4-1-3) Pyrazoles as key synthon in Synthesis of alkaloids

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Synthetic Photochemistry of sceptrin alkaloids: In a recent publication Professor Birman and one of
his colleagues reported a novel way to synthesize a molecule called dibromosceptrin
(C22H23Br4N10O2), shown here as in Scheme 49[157].
Scheme 49
5-Biological activities of pyrazoles
Pyrazoles are present in medicinally important compounds either for human being or for veterinary
medicine or other applications
5-1) Applications In human being medicine as in Fig.3
(a)Celecoxib ( 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide), it is a
highly selective COX-2 inhibitor[158-160].
(b) Lesopitron ( 2-{4-[4-(4-chloro-1H-pyrazol-1-yl)butyl]piperazin-1-yl}pyrimidine ), it is a selective
full agonist of the 5-HT1A receptor[161].
(c) Sulfaphenazole (4-amino-N-(1-phenyl-1H-pyrazol-5-yl)benzenesulfonamide Sulfaphenazole), it is
a sulfonamide antibacterial[162].
(d) O-12695 (4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-pentylpyrazole-3-carboxamide), it
acts as cannabinoid antagonist drugs [163-165].

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(e) Rimonabant 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-
pyrazole-3-carboxamide is an anorectic antiobesity drug[166] .
(f) VCHSR(5-(4-chlorophenyl)- 3-[(E)-2-cyclohexylethenyl]- 1-(2,4-dichlorophenyl)- 4-methyl- 1H-
pyrazole), it is a drug acts as a selective antagonist of the cannabinoid receptor CB1[167,168].
(g) Tebufenpyrad (N-(4-tert-Butylbenzyl)-4-chloro-3-ethyl-1-methylpyrazole-5-carboxamide or4-
Chloro-N-[[4-(1,1-dimethylethyl)phenyl]]methyl]-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide )is a
commonly used in commercial greenhouses[169].
(h) AM2511 (2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl)pyrazole-3-
carboxamide), it is an inverse agonist at the CB1 cannabinoid receptor[170].
(i) Betazole (2-(2H-Pyrazol-3-yl)ethanamine), it is a histamine H2 receptor agonist. as a gastric
stimulant [171,172].
(j) E-55888 (N,N-dimethyl-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenethylamine) it is anti-
hyperalgesic but not analgesic[173,174].
(b) (c)
(d) (e) (f)
(g) (h) (i)

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(j) Fig. 3
5-2) Applications In veterinary medicine as in Fig.4
Tepoxalin(3-[5-(4-Chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]-N-hydroxy-N-
methylpropanamide), it is a nonsteroidal anti-inflammatory drug approved for veterinary use (in
dogs)[175].
(b)Pyriprole(1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(difluoromethyl)thio]-5-[(2-
pyridinylmethyl)amino]-1H-pyrazole-3-carbonitrile) it is for veterinary use on dogs against external
parasites, fleas and ticks[176].
(c)Deracoxib4-[3-(Difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-yl]
benzenesulfonamide Deracoxib used in veterinary medicine to treat osteoarthritis in dogs[177].
(d) Mavacoxib (4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) it is a
veterinary drug used to treat pain and inflammation in dogs with degenerative joint disease[178]. It
acts as a COX-2 inhibitor[179].
(a) (b) (c)
(d) Fig.4
5-3) Applications In food chemistry as in Fig.5
(a) Yellow 2G ( Disodium 2,5-dichloro-4-[3-methyl-5-oxo-4-(4-sulfonatophenyl)diazenyl-4H-pyrazol-
1-yl]benzenesulfonate) it is a food coloring[180].
(b) Tartrazine (Trisodium (4E)-5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)hydrazono]-3-
pyrazolecarboxylate), it is used as a food coloring.[181-183].

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(b) (a)
Fig.5
5-3) Applications in pesticide as in Fig.6
(a) Fipronil RS (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
(trifluoromethylsulfinyl)-1H-pyrazole-3-carbonitrile), it is a broad-use insecticide[145,184,185].
(b) Isopropylmethylpyrazolyl dimethylcarbamate (1-Isopropyl-3-methyl-1H-pyrazol-5-yl
dimethylcarbamate), it is used as pesticide[186].
(b)
Fig.6
CONCLUSION:
In this review, we showed that over the past decades pyrazoles have achieved an important
place in the arsenal of organic chemists involved in the construction of complex molecules and natural
products as well as biologically active molecules, Synthesis of Substituted or unsubstituted pyrazole
has employed a great interest either by classical methods or by using palladium catalysed
reactions.Finally, one can reasonably anticipate that future studies will provide new applications to the
preparations of complex molecules , particularly in the area of biologically active compounds.
ACKNOWLDGEMENT:
The authors would like to thank the Chemistry Department, Cairo University, for providing the
research facilities The author wishes to express his most sincere thanks and full gratitude to Prof. Dr.
Ahmad M. Farag and Mr Mahmoud H. Yousef.

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