SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW PYRAZOLE DERIVATIVES

SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW PYRAZOLE DERIVATIVES

Mohamed A. Hamed ², Ahmed A. El Gokha¹, Ramzy Essam R. Abdelwahed ¹, Asem A. Mohamed ³, Abdel Moneim EL-Torgoman ¹ and Ibrahim El-Tantawy El Sayed ^*1

Chemistry Department ¹, Faculty of Science, El-Menoufeia University, Shebin El-Kom, Egypt.

Chemistry Department ², Faculty of Science, Tanta University, Tanta, Egypt.

Department of Chemistry of Natural and Microbial Products ³, National Research Center, Elbehosst., Dokki, Cairo, Egypt.

ABSTRACT: The synthesis of a novel of pyrazole derivatives was achieved by condensation of acetyl furan with phenyl hydrazine to give hydrazone (1) On the other hand, cyclization of α, β-unsaturated ketone. Using Vilsmeier reagent by DMF (dimethylformamid) and POCl₃ Phosphorusoxychloride) to give compound (2). The chemical structures of allnew compounds were established by IR, ¹HNMR, and mass spectra data. All the synthesized compounds were screened for in vitro antibacterial activity and most of them showed potency against both gram positive and gram negative bacteria. Compounds 4-(α-benzoyl aminoacrylic acid) – 3 - Furayl-1-phenylpyrazol, 4 - (α-benzoylaminomethylacrylate)-3-Furayl-1-phenylpyrazol, 4- (2-4-dinitrophenylhydrazone)-3-Furayl-1-phenylpyrazole showed the highest antibacterial activity against Bacillus subtilis strain with minium inhibition zone 19 mm.

Acetylfuran, Phenylhydrazine, Vilsmeier-Haack Reaction,

Antimicrobial activity

INTRODUCTION: Pyrazole symbolizes a class of simple aromatic ring organic compounds of the heterocyclic series which is a 5-membered ring skeleton composed of three carbon and two nitrogen atoms. Ludwig Knorr was the first who coined the term pyrazole in 1883. In 1959, the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from seeds of watermelons ^1-2. A bulk of literature is available to show the biological versatility such as anti-inflammatory ³, antibacterial ^4-5, anti-convulsant ⁶, anticancer ^7-8, anti-depressant ⁹, anti-hyperglycemic ¹⁰, antiviral ¹¹, antipyretic ¹², antioxidant ¹³, ant tubercular ¹⁴, fungicides ¹⁵, and analgesic activities ¹⁶.

These pyrazoles have also found applications in Transition-metal chemistry as an analytical reagent ¹⁷. Pyrazoles are weak mono-acidic-bases, formatting with mineral acid salts which dissociate in a vacuum and hydrolyse in water.

The ring system is more stable and less reactive than that of pyrrole. N-Phenyl group being replaced by hydrogen, although C-phenyl groups (unless aminated or hydroxylated) There are number of attempts to accomplish their separation through ions formed by addition or loss a proton, or as a result of the association, which is indicated by cryoscopic measurements and by the higher boiling point of isomer sun substituted nitrogen¹⁸.

MATERIALS:

Determinations of melting points were performed in open glass capillaries using electro thermal BUCHI (B-540) hot storage melting-point apparatus and are uncorrected. Infra-red (IR) spectra were recorded on a Shimadzu 435 Spectrometer, using KBr discs and values were represented in cm^-1 at the Micro analytical Center, Cairo University. (MS) Mass spectra were run on Shimadzu QP-2010 spectrometer and Mass spectra were run on Hewlett Packard 5988 spectrometer at the Micro analytical Center, Cairo University, Egypt. ¹HNMRspectrawas recorded on Bruker (300MHz) FT-NMR spectrometer using DMSO and the chemical shifts are given in δ (ppm) using tetramethylsilane (TMS) as an internal standard. Splitting patterns were designated as follows: s: singlet; d: doublet and m: multiplet.

The biological activity analysis was carried out at, Division of Pharmaceutical Industries, National Research Center, Cairo, Egypt. the compounds was made by thin layer chromatography (TLC) on silica gel-precoated aluminum sheets and the spots were detected by the aid of iodine vapour and by exposure to UV lamp at λ₂₅₄ nm for few seconds. Starting materials, MeOH, DMF, POCl₃, hexane and diethyl ether were either commercially available as reported in literature.

Synthesis of 1-phenyl-3-Furayl pyrazole-4-carbaldehyde (2):

Mixture of  (0.01 mole) of acetyl furan , and  (0.01 mole) of phenylhydrazine in 10ml Ethanol was refluxed in water bath for 4 h. the reaction mixture was cooled .the solid formed dried and crystallization from diethyl ether the formed of hydrazones (l) Show the following data; yellow color solid , Yield= 66.9%, MP. =75-73 ^ºC, and Mixture of 2.0gm (0.01 mole) of (I) Vilsmeier reagent, and 0.73 gm (0.01 mole) of DMF(di methyl form amid), 1.53gm (0.01 mole) of POCl₃ (Phosphorusoxychloride) was added drop wise with mechanical stirring for five hour. The reaction mixture was refluxed for six hours at 70-80^oC, then hydrolyzed on ice/water mixture, and neutralized by 5% NaOH Solution till pH4, the reaction mixture was cooled. The solid formed was filtered, washed with water, dried and crystallization from isopropanol. Show the following data Mp. 252-3 ^ºC; Yield: (90.2%), Infra-red spectra of compound (2) show: ν_C=Oofald.1667.16,ν_C=N1602.56, ν_C=C 1510.89, ν_{C-Hof 2 adj.H}820.02  and ν_{C-Hof 5 adj.H} 731.10 cm^-1, ¹HNMR (DMSO, 300 MHz) δppm=10.13 (s,1H,CHO), 9.31 (C-H Pyrazole), 6.54– 7.95 (m, 8H,Ar- H ), The mass spectra show the molecular ion peak at m/e = 238 [M]⁺ ,78 %)The base ion peak at m/e=77 [M]⁺ (-C₈H₅N₂O,100%),m/e= 209[M]⁺ (- CHO,15.2 %), m/e=237[M]⁺(-H,74%), m/e=210[M]⁺(-CO ,20%).

General method for preparation of compounds 3a, 3b:

Mixture of 0.24gm (0.001 mole) of compound (2), 0.18 gm, (0.001 mole) of benzoyl glycine ,0.12 gm. (0.001 mole) acetyl glycine and 0.04 gm.(0.001 mole) of sodium acetate in 5ml acetic anhydride. Was refluxed for two hours. The reaction mixture was cooled. hydrolyzed on ice/water. The solid formed was filtered, washed with water till pH7, then dried, crystallization from carbon tetrachloride.

Synthesisof 4 - [2' - Phenyl-5'(4'H)-oxazolonyl methylidene]-3-Furayl-l-phenylpyrazole(3a):

Show the following data; MP. =206 -7 ^ºC Yield= 78.7%, Infra-red spectra of compound (3a) show: ν_C=O1782.37, ν_C=C1639, ν_C=N 1588.49 and ν_C-O1227.4 cm^-1 , ¹HNMR (DMSO-300 MHz): δ ppm = 8.1(m,2H,C-HPyrazole),7.94(m,2H,Ph-H),7.87 (m,3H,Ph-H),7.27– 7.64 (m, 5H, Ar-H),7.15 (CH=CH), The mass spectra show the molecular ion peak at m/e = 381 [M]⁺ ,75 %)The base ion peak at m/e = 77[M]⁺ (- C₁₇H₁₀N₃O₃ ,100 %),m/e=337 [M]⁺(-CO₂,30.2%),m/e= 314 [M]⁺(-C₄H₃O,15.5%), m/e=222[M]⁺ (-C₉H₅NO₂ ,4.3%) .

Synthesis of 4-[2' -methyl-5'(4'H)-oxazolony lmethylidene]-3-Furayl-l-phenylpyrazole(3b):

Show the following data; MP. =147-8 ^ºC Yield= 84.6%, Infra-red spectra of compound (3b) show: _νC=O 1720.73, _νC=C 1605, _νC=N 1518.49 and _νC-O 1237.3 cm^-1, The mass spectra show the molecular ion peak at m/e = 319 [M]⁺, 2.1 %) The base ion peak at m/e = 237[M]⁺ (- C₃NO₂ ,100 %), m/e=248M]⁺(-C₃H₃O₂,4.5%), m/e = 222 [M]⁺ (-C₄H₃NO₂,5.3%),m/e=77[M]⁺ (-C₁₂H₈N₃O₃,55.3%, m/e=67[M]⁺ (-C₁₄H₁₀N₃O₂ ,30.2%).

General method for preparation of compounds 4a, 4b:

Mixture of 0.23gm (0.00065 mole) of compounds (3a, 3b), and 0.026 gm. (0.00065 mole) sodium hydroxide in 25ml ethanol was refluxed for three hours. The solution was concentrated, diluted with 100 ml water and acidified with 2% solution HCL. The solid formed was filtered, washed with water, then dried and crystallization from ethanol.

Synthesis of 4-(α-benzoyl aminoacrylic acid)-3-Furayl-1-phenylpyrazol (4a):

Show the following data; MP. =209-10 ^ºC Yield= 62.4%, Infra-red spectra of compound (4a) show: _ν-NH 3324_{, νC=OofPh}1682_{νC=Oof acid} 1628, _νC=N 1576, and _νC=C1561.62cm^-1, ¹HNMR (DMSO-300 MHz): δ ppm = 10.43(C-H acid),8.43 (m,3H,Ph-H),8.1(C-H Pyrazole),7.2– 7.96 (m,5H,Ar-H), The mass spectra show the molecular base ion peak at m/e = 399[M]⁺ ,100 %), m/e = 382 [M]⁺(- OH ,35 %),m/e=354 M]⁺(-COOH,10.6%), m/e = 95 [M]⁺ C₁₉H₁₄NO₃, 7.3%), m/e=77[M]⁺ (-C₁₇H₁₂N₃O₄,86%).

Synthesis of 4-(α-acetylaminoacrylic acid)-3-Furayl-1-phenylpyrazol (4b):

Show the following data; MP. =152-3 ^ºC Yield= 91.2%, Infra-red spectra of compound (4b) show: _ν-NH 3324, _{νC=Oof CH3} 1688,_{νC=Oof acid} 1632, _νC=N 1580 and_νC=C 1565cm^-1,The mass spectra show the molecular base ion peak at m/e = 337 [M]⁺ ,100 %), m/e = 320[M]⁺ (- OH ,40.5 %), m/e=292 [M]⁺ (-COOH, 14.3%) , m/e= 279 [M]⁺(-C₂H₄NO,7.2%), m/e=77[M]⁺(- C₁₂H₁₀N₃O₄ ,73.8%).

Synthesis of 4-(α-benzoylaminomethyl acrylate)-3-Furayl-1-phenylpyrazol (5):

A suspension containing  (0.0005 mole) of compound  (3a), 0.19 gm. in 25 ml methanol and  0..04gm (0.0005mole) sodium acetate .was refluxed for 30 hours. The solution was concentrated and cooling, the solid formed was filtered, and crystallization from ethanol, Show the following data MP. = 222-3^ºC Yield = 82.2%, Infra-red spectra of compound (5) show: _ν-NH 3323,_νC=OofPh 1761, _{νC=Oof ester} 1720, _νC=N 1674, and_νC=C 1561cm^-1,¹HNMR (DMSO-300 MHz): δ ppm = 8.1(C-H Pyrazole) ,7.4– 8.2 (m,5H,Ar-H),6.64 (CH=C), 3.77(s,3H, CH3), The mass spectra show the molecular ion peak at m/e = 413 [M]⁺ , 9.4 %) The base ion peak at m/e = 95[M]⁺ (- C₂₀H₁₆NO₃ ,100 %), m/e=382 [M]⁺ (-OCH₃, 8.5%), m/e= 308 [M]⁺ (C₇H₅O,1.2%), m/e = 222[M]⁺(-C₁₀H₉NO₃,4.1%), m/e=67[M]⁺(-C₂₀H₁₆N₃O₃,48.2 %).

 Synthesis of 4-(α-benzoylaminoacrylic acid hydrazide)-3-Furayl-1-phenylpyrazol (6):

A Mixture of 0.31 gm. (0.0008mole) of compound (3a). And 0.0008 ml (0.0008 moles) of 50% hydrazine hydrates in 20ml ethanol. Was refluxed for eight hours. The solution was concentrated and cooling, the solid formed was filtered, and crystallization from ethanol, Show the following data MP. = 204-5 ^°C, Yield = 75.6%, Infra-red spectra of compound (6) show: _νC-NH 3431, _νNH2 3280, _νC=O 1668, _νC=N 1622 and _νC=C 1554 cm^-1,¹HNMR (DMSO-300 MHz): δ ppm = 8.4(C-H Pyrazole) ,7.2– 8.3 (m, 5H,Ar- H) ,6.54 (CH=C),1.9(-NH₂),The mass spectra show the molecular ion peak at m/e = 413 [M]⁺ ,33 %) The base ion peak at m/e = 77[M]⁺ (- C₁₇H₁₄N₅O₃ ,100 %), m/e=397 [M]⁺ (-NH2, 3.5%) , m/e= 354 [M]⁺(-CH₃N₂O ,1.2%), m/e=293 [M]⁺ (-C₇H₆NO₃, 20%) , m/e=67[M]⁺(-C₁₉H₁₆N₅O₂,63%).

Synthesis of α, α^—bis ((3-Furayl-1-Phenyl pyrazolyl) -4-methylidene) cyclohexanone: (7)

A mixture of 0.2gm (0.00085 mole) of compound (2),and  0.17 ml. (0.0017 mole) cyclohexanone in 50% aqueous (DMSO) dimethylsulphoxide and 10 ml sodium hydroxide was stirred at 100^oC for five hours. After cooling and neutralization with diluted HCL.  The solid formed was filtered, washed with water, then dried and crystallization from ethanol, Show the following data MP. = 273-4^°C, Yield = 83 %, Infra-red spectra of compound (7) show: _νC=C 3055, _νC=O 1659and _νC=N 1628cm^-1, ¹HNMR (DMSO-300 MHz): δ ppm = 8.43(s,C-H Pyrazole) ,8.41(D,CH=CH),7.1– 7.42 (m, 5H,Ar-H),1.55 (t,2H,CH₂), The mass spectra show the molecular ion peak at m/e = 538 [M]⁺ ,15.6 %)The base ion peakatm/e=67[M]⁺(-C₃₀H₂₃N₄O₂,100%),m/e=510 [M]⁺(-CO, 23%), m/e=444 [M]⁺(-C₆H₆O ,20.6%), m/e=222 [M]⁺ (-C₂₀H₁₆N₂O₂, 4%), m/e=95[M]⁺(-C₃₀H₂₃N₂O₂,4.3%).

Synthesis of 4-(2^-4^--dinitrophenylhydrazone)-3-Furayl-1-phenylpyrazole (8):

A mixture of 0.083 gm (0.00085 mole). of concentrated sulphuric acid H₂SO4 was added coutiosouly to a suspension of 0.17 gm (0.00085mole) 2.4dinitrophenyl hydrazine(DNP) in 10 ml methanol. The solution was wormed and filtered. And 0.2 gm (0.000085 mole) of compound (2) was added to the filtrate with stirring. The solid formed was filtered, and crystallization from ethanol, Show the following data MP = 281-2 ^◦C, Yield = 87.2%, Infra-red Spectra of compound (8) show:_ν-NH3230 ,_νC=N 1612, _νC=C 1524, _{νC-H of 2 adj.H} 815and _{νC-H of 5 adj.H} 724 cm^-1, ¹HNMR (DMSO-300 MHz):δ ppm = 7.2-8.4 (m,5H, Ar- H), 8.6(CH=N), 7.1 (-NH)The mass spectra show the molecular ion peak at m/e=418[M]⁺,32.6 %)The base ion peak at m/e = 67 [M]⁺(- C₁₆H₁₁N₆O₄ ,100 %), m/e=372 [M]⁺(-NO₂, 76.1%),m/e=326 [M]⁺(-N₂O₄,65.3%), m/e=222 [M]⁺ (-C₆H₄N₄O₄,3.2%), m/e=95[M]⁺(-C₁₆H₁₁N₄O₄,3.4%).

Synthesis of 4-[(2'-Phenyl-2'-imidazolin-5'-onyl)methylidene]-3-Furayl-l­ phenylpyrazole(9)

A Mixture of 0.2gm (0.00085 mole) of compound (2), and 0.27 gm. (0.0017 mole) of  benzamidine hydrochloride dehydrate  and 0.2 gm. (0.0017 mole) of Ethylchloroacetate in 20ml n- propanol . Was refluxed with strring for one hours. The solid formed was filtered, washed with methanol, water, and finally with methanol, then dried and crystallization from n-butanol, Show the following data MP. = 324-5^◦C, Yield = 92.8 %, Infra-red spectra of compound (9)_νc-NH 3105, _νC=O1705,_νC=C 1640and _νC=C 1640cm^-1,1HNMR ( DMSO-300 MHz): δ ppm = 8.43 (s,C-H Pyrazole) ,8.01(-NH),6.98– 7.86 (m, 13H, H aroma), The mass spectra show the molecular ion peak at m/e = 380 [M]⁺ ,39.2 %)The base ion peak at m/e = 67[M]⁺ (- C₁₉H₁₃N₄O, 100%),m/e=352[M]⁺(-CO, 5.9%), m/e=248 [M]⁺(-C₈H₆NO,13.6%),m/e=222[M]⁺ (-C₉H₆N₂O, (20.3%), m/e = 95[M]⁺ (- C₁₉H₁₃N₂O, 45.2%).

Synthesis of   4, 3^-[(6^-Amino-5^--cyano-4^- -phenyl] -3-Furayl-1-phenylpyrazole (10):

A Mixture of 0.03gm (0.000125 moles) of compound (2), and 0.008 gm. (0.000125 mole) of malononitrile and in 20ml absolute ethanol and few drops of piperidine were refluxed for four hours.  After cooling the separated solid was filtered, dried, and crystallization from ethanol, Show the following data MP. = 204-5^◦C. Yield = 89.4 %, The spectra of compound (10) show ¹HNMR (DMSO-300 MHz): δ ppm = 8.43(s, C-H Pyrazole), 7.86– 7.45 (m, 8H, H aroma), 6.98 (D, CH=CH), The mass spectra show the molecular ion peak at m/e = 286 [M]⁺ ,16.2 %) The base ion peak at m/e = 67[M]⁺ (-C₁₃H₇N₄, 100%), m/e=285[M]⁺(-H, 33.2%),m/e=260 [M]⁺(-CN,52.1%),m/e=259[M]⁺ (-HCN, (13.2%), m/e = 95[M]⁺ (- C₁₃H₇N₂,6.2%).

RESULTS AND DISCUSSION: 

Substituted phenyl hydrazines were prepared by heating substituted a acetyl furan with different hydrazines in methanol under reflux for 4-5 h. Vilsmeier-Haack reaction of phenyl hydrazines using DMF and POCl₃ afforded 1-phenyl-3-Furayl pyrazole-4-carbaldehyde in good yields and in high purity. The structures were confirmed on the basis of IR, ¹HNMR and mass spectral data according to scheme(1).

The aldehyde (2)  were converted into 4-[2' -Phenyl-5'(4'H)-oxazolonylmethylidene]-3-Furayl-l-phenylpyrazole(3a) and 4-[2' -methyl-5'(4'H)-oxazolonyl methylidene] - 3- Furayl - l-phenyl pyrazole (3b) to react with benzoyl glycine ,acetyl glycine in presence  of sodium acetate in 5ml acetic anhydride The structures were confirmed on the basis of IR, ¹H NMR and mass spectral data according to scheme (2) and the end product (3a, 3b) to hydrolysis with sodium hydroxide to yield4-(α-benzoyl aminoacrylic acid)-3-Furayl-1-phenyl pyrazol(4a)4-(α-acetylaminoacrylicacid)- 3-Furayl-1-phenylpyrazol(4b)The structures were confirmed on the basis of IR, ¹H NMR and M.S. data according to scheme (2).

And the hydrolysis  of compound (3a) with sodium acetatetoformed4-(α-benzoylaminomethylacrylate)-3-Furayl-1-phenylpyrazol(5) and react with hydrazine hydrate to formed the 4-(α-benzoylaminoacrylic acid hydrazide) – 3 - Furayl-1-phenylpyrazol(6)The structures were confirmed on the basis of IR, ¹HNMR and M.S. data according to scheme (3)

and  The aldehyde (2)  were converted into α, α^--bis((3-Furayl-1-Phenylpyrazolyl) – 4 -methylidene) cyclohexanone(7), 4-(2-4—dinitrophenyl hydra zone) -3-Furayl-1-phenylpyrazole (8) to react with cyclohexano n in 50% aqueous (DMSO) dimethyl sulphoxide , concentratedsulphuricacidH₂SO4and .4dinitrophenyl hydrazine(DNP) The structures were confirmed on the basis of IR, ¹H NMR and mass spectral data according to scheme (4)

and  The aldehyde (2)  react with benzamidine hydrochloride dehydrate  and Ethylchloroacetate  , malononitrile to formed the compounds 4-[(2'-Phenyl-2'-imidazolin-5'-onyl) methylidene]-3-Furayl-l­ phenylpyrazole(9) 4, 3-[(6-Amino-5--cyano-4- -phenyl]-3-Furayl-1-phenylpyrazole (10) The structures were confirmed on the basis of IR, ¹HNMR and mass spectral data according to scheme (5)

A possible mechanism for cyclization along with formylation of pyrazole is outlined in scheme (6). The proposed mechanism is initial electrophilic attack of Vilsmeier-Haack reagent (A) on hydrazone(1) yielded the intermediate (B)which subsequently losses amolecule of HCl to provide intermediate (C). The nucleophilic attack by N-H group initiates the cyclisation and the resulting pyrazole intermediate losses Me₂NH to give the more stable pyrazole derivative (D). The pyrazole (D) react with another molecule of V.H. reagent (A) in an electrophilic substitution process giving an minimum salt (E), which is hydrolysed to corresponding 4-formyl pyrazole (2) as depicted in scheme (6), In summary the electrophilic attack of first Vilsmeier –Haack (VH) complex at the probable attacking site of hydrazones results into cyclisation. While electrophilic attack of second (VH) complex forms formyl product after hydrolysis. Finally intra molecular (1,5) hydrogen shift, cyclisation and elimination of NHMe₂ to give pyrazole derivative with this series of pyrazole aldehydes in hand.

Antimicrobial screening:

The antibacterial activities of the synthesized compounds were tested against Escherichia coli NRRL B-210 and Pseudomonas NRRL B-23 (Gram -ve bacteria), Bacillus subtilis NRRL B-543 and Staphylococcus aureus NRRL B-313 (Gram +ve bacteria) using nutrient agar medium. The antifungal activity of these compounds was also tested against Candida albicans NRRL Y-477 using Sabouraud dextrose agar medium.

Agar Diffusion Medium:

The synthesized compounds were screened in vitro for their antimicrobial activity against, by agar diffusion method (Cruickshank et al.1975). 0.5 ml suspension of each of the aforementioned microorganisms was added to sterile nutrient agar media at 45°C and the mixture was transferred to sterile Petri dishes and allowed to solidify. Holes of 0.9cm in diameter were made using a cork borer. Amounts of 0.1ml of the synthesized compounds were poured inside the holes. A hole filled with DMSO was also used as control. The plates were left for 1 hour at room temperature as a period of pre-incubation diffusion to minimize the effects to variation in time between the applications of the different solutions.  The diameters of the inhibition zone of were measured and compared with that of the standard and the values were tabulated. The same method was carried out using Sabouraud dextrose agar medium on using Candida albicans NRRL Y-477. The plates were then incubated at 30°C for 24 hours and observed for antibacterial activity. The diameters of inhibition zone were measured and compared with that of the standard, the values were tabulated. Ciprofloxacin (50µg/ml) and Fusidic acid (50µg/ml) were used as standard for antibacterial and antifungal activity respectively ^19-21. The observed zone of inhibition is presented in Table 1.

TABLE 1: IN VITRO ANTIMICROBIAL ACTIVITY BY AGAR DIFFUSION METHOD OF TESTED COMPOUNDS

Highly active (+++)=  (inhibition zone > 17 mm)

Moderately active (++)=(inhibition zone 12 - 16 mm)

Slightly active (+)=  (inhibition zone 8 - 11 mm)

Inactive (-ve) =  (inhibition zone < 8 mm)

CONCLUSION: In the present study, our attention was focused on the synthesis and antimicrobial, antifungi evaluation of pyrazol derivatives compound. The antimicrobial activity of compounds 3b,4a, 5,8 indicated Highly activity against Bacillus subtilis (Gram +ve bacteria) and moderate activity to compounds 2,3a,4b, 6,7,9 and the compound 2,3a,3b,7 the Highly activity against against E coli (Gram -ve bacteria) while  the compounds 4a,4b,5,6,8,9 moderate activity. And the antifungal activity the compounds 5,8 is highly activity against Candida albicans while the compunds 2,3a,3b,4a,4b,6,7,9 is moderate activity.

ACKNOWLEDGEMENT: The authors are thankful to the Department of organic chemistry of Menoufia University, Egypt for providing literature survey facility to carry out the work.

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    How to cite this article:

    Md. Hamed A, El Gokha AA, Abdelwahed RER, Mohamed AA, EL-Torgoman AM and El-Tantawy El Sayed I: Synthesis and biological evaluation of some new pyrazole derivatives. Int J Pharm Sci Res 2016; 7(11): 4414-21.doi: 10.13040/IJPSR.0975-8232.7(11).4414-21.

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