INTRODUCTION:

Pyrazoline derivatives have been found to possess a broad spectrum of biological activities such as tranquillizing, muscle relaxant, psychoanaleptic, anticonvulsant, antihypertensive and antidepressant activities^1-6. Among various pyrazoline derivatives, 2-pyrazolines seem to be the most frequently studied pyrazoline type compounds. It was found that benzene sulfonamide moiety has exhibited its importance by its presence in a large variety of pharmaceuticals covering a wide range of biological activities. So it was thought worthwhile to synthesize new compounds having combination of pyrazoline nucleus and benzene sulfonamide group. In 1998, Powers et al. ⁷ reported that the reaction of chalcones and phenyl hydrazine hydrochloride in the presence of sodium hydroxide was carried out in the absolute ethanol at 70°C, but there is a disadvantage of longer reaction time (8 hr). So, keeping in view the environmental concerns, the title compounds were synthesized by using ultrasound irradiation, as one the tools of green chemistry¹.

Ultrasound has increasingly been used in organic synthesis in the last three decades^8-10. Compared with traditional methods, the procedure is more convenient and easily controlled. A large number of organic reactions can be carried out in higher yield, shorter reaction time or milder conditions under ultrasonic irradiation. However, the use of ultrasound in heterocyclic systems is not fully explored^11-13. In order to expand the application of ultrasound in the synthesis of heterocyclic compounds, we herewith report a general, eco friendly and efficient method for the synthesis of 4-(3,5-diaryl substituted)-4,5-dihydro-1H-pyrazol-1-yl ) benzene sulfonamide.

MATERIAL AND METHOD:

Chemistry:

Melting points were determined in open capillaries and were uncorrected. The IR spectra were recorded on Jasco FTIR-4000 and Bruker Daltonics; NMR spectra were recorded on Bruker Advance 200 MHz spectrometer using CDCl₃ and DMSO as solvent with TMS as an internal standard. Mass spectra were obtained on Bruker Daltonics ESI-MS. Elemental analysis was determined by using a Perkin–Elmer 240c elemental analysis instrument and the results obtained were within ± 0.4 % of the theoretical values. Sonication was performed in a Bandalein Sonorex Ultrasonic cleaner at 65°C with a frequency of 40 kHz and a nominal power 250 W. The reaction flask was located in the water bath of the ultrasonic cleaner and the temperature of the water bath was controlled at 65°C. Some reactions were performed using ultrasonic processor VCX -500 (Probe type) 500 W 220 V .The novel 3,5-diaryl 1-(4-sulfamylphenyl) 2-pyrazolines 6a-j have been synthesized in five steps as outlined in Scheme1.The characterization data such as time required for Ultrasound method and the R_fvalues of the synthesized compounds is given in Table 1.

Scheme 1

Table 1 Characterization data of 3,5-diaryl 1-(4-sulfamylphenyl) 2-pyrazolines 6(a-j)

Compd	R	M.W.	Time (min)	R_f*
6 a		471.96	50	0.78
6b		527.59	60	0.58
6c		482.51	50	0.84
6d		467.54	70	0.58
6e		443.54	60	0.72
6f		427.47	65	0.76
6g		437.51	70	0.65
6h		497.56	70	0.72
6i		480.58	55	0.61
6j		453.51	50	0.70

*Solvent system: (n-Hexane: Ethyl acetate: 8:2)

Experimental protocols

Step1 Synthesis of 1-(2,4-dimethoxyphenyl)ethanol 2 .

In a 3- necked R.B.F, dry magnesium metal (1.5 g) and a small quantity of iodine in dry diethyl ether was taken and stirred at room temperature for few minutes. Methyl iodide (2 g) was then added slowly into the reaction mixture .The colour of iodine discharges indicating the formation of Grignard reagent. The reaction was continuously stirred for 15-30 minutes at room temperature. In another R.B.F 2,4 dimethoxy benzaldehyde (0.1 mole) was dissolved in dry diethyl ether and added drop wise to the above reaction mixture and was stirred for 30 minutes at room temperature. The reaction was monitored by TLC. After completion of the reaction, saturated solution of ammonium chloride was added drop wise and the reaction mixture was extracted with ether. After evaporation of the solvent product 1-(2,4-dimethoxyphenyl) ethanol was obtained. Yield = 54%. m.p. =182˚C.

Step 2 Synthesis of 1-(2, 4-dimethoxyphenyl) ethanone 3.

In a 3- necked R.B.F, dry magnesium oxide (5 g) and dry benzene (10ml) were stirred for few minutes. To this reaction mixture, 1-(2, 4-dimethoxyphenyl) ethanol (1gm) in dry benzene was added. The reaction mixture was refluxed for 2 hr at 80˚C. The solid obtained was filtered and washed with ether. Yield = 64%,m.p. =212˚C.

Step 3 Synthesis of substituted prop-2-en-1-ones 4.

Equimolar quantities of 2, 4-dimethoxy acetophenone (0.01mole) and substituted aromatic aldheyde (0.01 moles) was dissolved in ethanol (30ml) and a cooled solution of NaOH (15ml, 40%) was added in portions keeping the temperature below 10ºC with continuous stirring. The reaction mixture was kept overnight at room temperature. It was then acidified with dilute HCl and poured over crushed ice with continuous stirring. The product obtained was filtered, washed with cold water, dried and recrystallized from ethanol. Yield = 64%, m.p. =212˚C.

Step 4 Synthesis of 4-hydrazinylbenzenesulfonamide hydrochloride. 5

A cold (0-5⁰C) stirred mixture of sulfanilamide (34.2 g , 0.2 mole), hydrochloric acid, (100 ml) and crushed ice (200g) was diazotized by the drop wise addition of sodium nitrite (14g, 0.2mole) in water (25ml) over 30 minutes .The cold diazonium salt thus formed was rapidly added to a well cooled (0-5⁰C) solution of stannous chloride (100g) in hydrochloric acid (150 ml) with vigorous stirring and the resulting mixture was kept in ice bath. The precipitated 4-hydrazinobenzenesulfonamidehydrochloride was filtered and washed with minimum quantity of cold methanol. m.p. = 220⁰C

Step 5 Synthesis of 4-(3, 5-diaryl substituted)-4, 5-dihydro-1H-pyrazol-1-yl ) benzene sulfonamide.6(a-j)

A mixture of substituted prop-2-ene-1-one (0.01mol) in ethanol, hydrazine hydrate (0.01 mole) and acetic was added in a 50 ml conical flask and was irradiated under ultrasound in an open vessel at 65⁰C until completion of the reaction (50-90 min.). The reaction was monitored by TLC. The reaction mixture was poured into crushed ice and the precipitated solid was collected. The precipitate was separated by filtration, washed with water and recrystallized from ethanol.

Characterization data of synthesized compounds 6(a-j)

1) 4-(5-(4-chlorophenyl)-3-(2, 4-dimethoxyphenyl)-4, 5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6a.

Yield=78% m.p.= 118⁰C ; IR 3381 cm^-1 and 3262 cm^-1(NH₂),1592 cm^-1 (C=N),1332 cm ^-1 and 1156 cm ^-1 (SO₂N<) ; PMR (200 MHz,CDCL3, δ in ppm) 2.92(1H,dd ,J=5.62 Hz ,18.11 Hz, H-4 trans (pyrazoline),3.57(3H,s,OCH₃),3.65(3H,s,OCH₃ ),3.64[(1H,dd, J=11.16 Hz, 18.14 Hz, H- cis(pyrazoline)], 5.21 (2H,s,SO₂NH₂), 5.64 [1H, dd, J=5.24Hz, 12.0 Hz, H-5(pyrazoline)],6.62(1H,d,J=2.18Hz,H-3’),6.82(1H,dd,J=1.68Hz,8.24Hz,H-5’), 7.24 (2H, d, J=8.41Hz,H-3”,H-5”),7.39(2H,d,J=8.84Hz,H-3,H-5), 7.48(2H,d,J=8.46 Hz,H-2,H-6),7.67 (2H,d,J=8.28Hz,H-2”,H-6”),7.87(1H,d,J=8.46Hz,H-6’);ESI(MS)=472.

Anal. Calcd. for C₂₃H₂₂ClN₃O₄S cal/found: C = 58.53/58.50, H= 4.70/4.65, N= 8.90/8.88, O= 13.56/13.50, S= 6.79/6.66, Cl = 7.51/7.46

2) 4-(3-(2,4-dimethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide 6b

Yield= 84%. m.p.= 233⁰C; IR 3329 cm^-1 and 3235 cm^-1(NH₂),1594 cm^-1 (C=N),1338 cm ^-1 and 1157 cm ^-1 (SO₂N<) ; PMR (200 MHz,CDCl₃, δ in ppm) 3.18[1H,ddJ=6.52Hz, 10.91Hz, , H-4 trans (pyrazoline)], 3.62-3.72 (12H,s,4xOCH₃), 3.84(3H,s,OCH₃,), 3.87 [1H,dd, J=12.25Hz,18.0Hz,H-4(pyrazoline)], 4.65[1H,dd, J= 6.28Hz,11.53Hz,H-5 (pyrazoline)], 5.92(2H,s,SO₂NH₂), 6.24(3H,s,H-3’, H-2, H-6), 6.711H,d, J=8.42Hz, H-5’), 7.16(2H,d, J=8.27Hz,H-3”,H-5”),7.27(2H,d,J=8.24Hz,H-2”, H-6”).7.57 (1H, d,J=8.47 Hz, H-6’) ; ESI(MS) =527. Anal. Calcd. for C₂₆H₂₉N₃O₇S cal /found: C = 59.19/59.15, H= 5.54/5.50, N= 7.96/7.94, O=21.23/21.19, S=6.08/6.03.

3) 4-(3-(2,4-dimethoxyphenyl)-5-(4-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6c

Yield=74% m.p.= 212⁰C ; IR 3342 cm^-1 and 3282 cm^-1(NH₂),1593 cm^-1 (C=N),1534 cm^-1 and 1350 cm^-1 (NO₂),1321 cm^-1 and1158 cm^-1 (SO₂N<); PMR (200 MHz,CDCl₃, δ in ppm) 3.46 [1H,ddJ=5.24Hz,17.82Hz, , H-4 trans (pyrazoline)],3.74 (3H,s, OCH₃), 3.82 (3H,s, OCH₃,), 3.97[1H,dd, J=12.16Hz, 18.02Hz, H-4cis(pyrazoline)], 5.26[1H,dd, J=5.46 Hz, 11.92Hz, H-5(pyrazoline)], 5.69(2H,s,SO₂NH₂), 6.58(1H,s,H-3’,H-2,H-6), 6.75(1H,d, J=8.24Hz,H-5’), 7.38(2H,d,J=8.16Hz,H-3”,H-5”), 7.52(2H,m,H-5,H-6), 7.72(2H,d,J=8.21 Hz, H-2”,H-6”), 7.84(1H,d, J=8.81Hz,H-6’), 8.24(2H,m,H-2, H-4);ESI (MS) = 482. Anal. Calcd. for C₂₃H₂₂N₄O₆S cal /found: C = 57.25/ 57.20, H=4.60/4.55, N=11.61/11.56, O=19.90/19.88, S=6.65/6.61.

4) 4-(3-(2,4-dimethoxyphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6d

Yield= 72% m. p.= 128 ⁰C; IR 3367 cm^-1 and 3272 cm^-1(NH₂),1596 cm^-1 (C=N),1336cm ^-1 and1156 cm ^-1 (SO₂N<); PMR (200 MHz,CDCl₃, δ in ppm) 3.18(1H,dd ,J=5.24 Hz ,18.76 Hz,. ,H-4 trans (pyrazoline), 3.64(3H,s,OCH₃), 3.72(3H,s,OCH₃) 3.79 (3H,s, OCH₃), 3.84[(1H,dd, J=12.04Hz,18.16HzH-4,cis(pyrazoline)], 4.78(2H,s,SO₂NH₂), 4.92 [1H, dd, J=5.42Hz, 11.36 Hz,H-5 (pyrazoline)], 6.52(1H,s,H-3’), 6.41(1H, d, J= 7.75 Hz, H-5’), 6.63 (2H,d,J=8.42Hz,H-3,H-5), 7.11(2H,d,J=8.24Hz,H-3”,H-5”), 7.17 (2H,d, J=8.12Hz, H-2,H-6),7.42(2H,d,J=8.67Hz,H-2”,H-6”), 7.42 (1H,d,J=8.30Hz, H-6’); ESI (MS) = 467. Anal. Calcd. for C₂₄H₂₅N₃O₅S cal/found: C=61.65/61.61, H= 5.39/5.37, N=8.99/8.95, O=17.11/17.09, S=6.86/6.81.

5) 4-(3-(2,4-dimethoxyphenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6e

Yield=79% m.p. = 165 ⁰C; IR 3340 cm^-1 and 3262 cm^-1(NH₂),1594 cm^-1 (C=N),1530 cm^-1 and 1350 cm^-1 (NO₂),1324 cm^- and1162 cm^- (SO₂N<); PMR (200 MHz,CDCL3, δ in ppm) 3.24(1H,dd ,J=5.62Hz ,18.14 Hz,. ,H-4 trans (pyrazoline), 3.48(3H,s,OCH₃), 3.61 (3H,s, OCH₃ ), 3.94[(1H,dd, J=11.96 Hz,18.13 Hz, H-4cis(pyrazoline)], 4.70 (2H, s, SO₂NH₂), 5.42[1H,dd,J=5.25Hz,12.0 Hz,H-5 (pyrazoline)], 6.42 (1H,d, J=1.98 Hz,H-3’), 7.19 (2H,d,J=8.61Hz,H_3”,H-5”), 7.26 (2H,d,J=8.27Hz,H-3,H-5),7.34 (2H, d, J=8.37 Hz, H-2,H-6), 7.87(2H,d,J=8.82Hz,H-2”, H-6”),7.94(1H,d, J=8.21 Hz, H-6’); ESI (MS) =444. Anal. Calcd. for C₂₁H₂₁N₃O₄S₂ cal/found: C =58.83/58.80, H= 4.94/4.90, N=8.95/8.90 O=13.63/13.60, S=13.66/13.61.

6) 4-(3-(2,4-dimethoxyphenyl)-5-(furan-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)benzene sulfonamide 6f

Yield= 84%. m. p.= 207⁰C; IR 3384 cm^-1 and 3246 cm^-1(NH₂), 1615 cm^-1(C=N), 1324 cm ^-1and 1135 cm^-1(SO₂N<); PMR (200 MHz,CDCl₃, δ in ppm) 2.65(6H,s,2x CH₃), 3.52[1H,dd,J=4.27Hz,18.18Hz, H-4 trans (pyrazoline)], 3.87(3H,s,OCH₃), 3.64 [1H,dd, J=11.69,18.09Hz, H-4 cis (pyrazoline)], 5.48[1H,m ,H-5(pyrazoline)],6.62-7.22 (10H, m, Aromatic protons and SO₂NH₂), 7.45(2H,d,J=8.67Hz,H-2”,H-6”), 7.86 (1H,d, J=9.25 Hz,H-6’); ESI(MS) =427. Anal. Calcd. for C₂₁H₂₁N₃O₅S cal/found :C =59.00/58.95, H=4.95/4.90 N=9.83/9.79, O= 18.71/18.69, S=7.50/7.45.

7) 4-(3-(2,4-dimethoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide 6g

Yield= 79%. m.p.= 189 ⁰C; IR 3299 cm^-1 and 3086 cm^-1(NH₂),1592 cm^-1 C=N),1321 cm^-1 and 1143 cm^-1 (SO₂N<) ; PMR (200MHz,DMSO,δ in ppm) 3.17[1H,.m, ,H-4 trans (pyrazoline)], 3.81 (3H,s,OCH₃), 3.98(1H,m,, H-4 cis(pyrazoline)],5.40[1H,m,H-5 (pyrazoline)], 6.62 (2H,s,SO₂NH₂), 7.00-7.34 (9H,m, aromatic protons), 7.55 (2H,d, J=8.32Hz,H-2”,H-6”), 7.85(1H,d,J=8.19Hz,H-6’); ESI(MS) =437. Anal. Calcd. for C₂₃H₂₃N₃O₄S cal/found: C = 63.14/63.10, H=5.30/5.25, N=9.60/9.56, O=14.63/14.56, S=7.33/7.30.

8) 4-(3,5-bis(2,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6h

Yield= 78% m. p. = 197⁰C. IR 3346cm^-1 and 3286 cm^-1(NH₂),1583 cm^-1 C=N),1515 cm^-1 and1350 cm^-1 (NO₂), 1320 cm^- and1140 cm^- (SO₂N<); PMR (200 MHz, CDCl₃, δ in ppm) 3.46(1H,dd ,J=5.24 Hz ,18.24 Hz,. ,H-4 trans (pyrazoline),3.77-3.83 (3H, s, OCH₃), 3.97[(1H,dd, J=12.24 Hz,18.16 Hz, H-4 cis(pyrazoline)], 4.24 (2H,s, SO₂NH₂), 4.62[1H,dd,J=5.81Hz,11.27 Hz,H-5 (pyrazoline)], 6.23(1H,s,H-3’), 6.53 (1H,d, J=7.14Hz,H-5’), 6.82(2H,d,J=8.61Hz,H-3, H-5), 7.04(2H,d,J=8.41Hz,H-3”, H-5”), 7.17 (2H, d,J=8.18Hz,H-2,H-6),7.74 (2H,d, J=8.42 Hz, H-2”,H-6”), 7.82 (1H,d,J= 8.24 Hz,H-6’); ESI(MS) = 497. Anal. Calcd. for C₂₅H₂₇N₃O₆S cal/found C =6.35/6.29, H=5.47/5.45, N=8.45/8.40, O=19.29/19.25, S=6.44/6.41.

9) 4-(3-(2,4-dimethoxyphenyl)-5-(4-(dimethylamino) phenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide 6i

Yield= 82%. m.p.= 195 ⁰C; IR 3318 cm^-1,3158 cm^-1 and 3069 cm^-1[NH₂ and N(CH₃)₂], 1594 cm ^-1 (C=N), and1338 cm ^-1 and1157 cm^-1 (SO₂N<); PMR (200 MHz, CDCl₃, δ in ppm) 2.91(6H,s, CH₃),3.27[1H,dd,J=4.24Hz,18.18Hz, ,H-4 trans (pyrazoline)],3.62 (3H,s, OCH₃), 3.81(3H,s, OCH₃), 3.92[1H,dd,J=11.61,18.09Hz,H-4 cis(pyrazoline)], 5.27 [1H,m , H-5(pyrazoline)],6.62-7.22(10H,m,Aromatic protons and SO₂NH₂), 7.55(2H,d, J=8.67 Hz, H-2”,H-6”),7.83(1H,d,J=9.25Hz,H-6’); ESI(MS) =480. Anal. Calcd. for C₂₅H₂₈N₄O₄S cal/found: C = 62.48/62.45, H=5.87/5.86, N=11.66/11.60, O=13.32/13.29, S=6.67/6.64.

10) 4-(3-(2,4-dimethoxyphenyl)-5-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzene sulfonamide 6j

Yield=85%. m. p =215 ⁰C; IR 3379 cm^-1 and 3254 cm^-1(NH₂),1599 cm^-1 (C=N),1338 cm^-1 and1147 cm^-1 (SO₂N<); PMR (200 MHz, DMSO, δ in ppm) 3.42(1H,dd ,J=5.21 Hz, 18.38 Hz, H-4 trans (pyrazoline),3.78-3.81 (9H,m,3XOCH₃), 4.25(1H,dd, J=12.17 Hz, 18.13 Hz, H-4 cis (pyrazoline),5.24[1H,dd,J=5.62 Hz,11.28 Hz,H-5 (pyrazoline)], 6.51(2H,m, H-3’, H-5’ ) 6.71(4H,m,SO₂NH₂, H-3’’, H-5’’ ),7.13(1H,dd, J=6.65 Hz, H-3 ),7.25(2H,m,H-4,H-5),7.61(1H,d,J=7.51Hz,H-6) 7.80 (2H,d, J=8.24 Hz,H-2”,H-6”), 7.87(1H,d,J=8.51 Hz,H-6’); ESI(MS) =453. Anal. Calcd. for C₂₄H₂₅N₃O₅S cal/found: C = 61.65/61.60, H=5.39/5.35, N=8.99/8.95, O=17.11/17.09, S=6.86/6.81.

Pharmacological Screening:

All the newly synthesized compounds were screened for anti-inflammatory activity by Carrageenan- induced rat hind paw edema¹⁴

Anti inflammatory Activity:

Carrageenan- induced rat hind paw edema

The method of winter et al (Winter et al 1962) was used with slight modification .The apparatus used for the measurement of rat paw volume was that of Butle et al, modified by Singh and Gosh .The animals were divided into different groups each containing 4 animals one group served as control, another group served as a standard (Indomethacin) and the rest of the groups were used for the test drugs.

The rats were dosed orally at 100mg/kg body weight, including the control and the standard. Test compounds and standard drug were suspended in 0.5 %sodium carboxy methyl cellulose mucilage, which was used as vehicle. For the control group a solution of 1% of carragenan was used as anti-inflammatory agent.

RESULTS AND DISCUSSION:

All the compounds were evaluated for their anti-inflammatory activity and have shown promising results. Carrageenan- induced rat hind paw edema investigated the anti-inflammatory activity of synthesized compound and results obtained are shown in Table 2.

Table .2: Anti-Inflammatory data of 3,5-diaryl 1-(4-sulfamylphenyl) 2-pyrazolines 6(a-j)

Compound

Paw volume (in ml) ±SEM

(% Inhibition)

1 hr

3 hr

5hr

Vehicle

0.68 ± 0.0014

0.75 ± 0.0026

0.75 ± 0.0045

Indomethacin (Std)

0.10 ± 0.0021

(85.29%)

0.15 ± 0.0031

(80.00%)

0.45 ± 0.0040

(40.00%)

0.15 ± 0.0062

(73.5%)

0.23 ± 0.0021

(69.3%)

0.25 ± 0.0022

(66.6%)

0.07 ± 0.0014

(89.7%)

0.13 ± 0.0031

(82.67%)

0.18 ± 0.0024

(76.67%)

0.30 ± 0.0012

(89.7%)

0.38 ± 0.0036

(49.3%)

0.67 ± 0.0026

(10.66%)

0.14 ± 0.0052

(79.4%)

0.18 ± 0.0042

(76%)

0.21 ± 0.0034

(72%)

0.45 ± 0.0016

(35.0%)

0.56 ± 0.0021

(25.3%)

0.72 ± 0.0046

(4.0%)

0.16 ± 0.0042

(76.4%)

0.23 ± 0.0026

(69.33%)

0.32 ± 0.0021

(69.33%)

0.09 ± 0.0016

(86.76%)

0.15 ± 0.0041

(80.00%)

0.15± 0.0046

(80.00%)

0.06 ± 0.0042

(91.17%)

0.13 ± 0.0024

(82.67%)

0.25 ± 0.0042

(66.67%)

0.05 ± 0.0037

(92.6%)

0.14 ± 0.0045

(81.3%)

0.19 ± 0.0024

(74.66%)

0.07 ± 0.0028

(89.70%)

0.16± 0.0036

(78.6%)

0.34 ± 0.0056

(54.66%)

Dose = 100 mg/kg of body weight. (Std. and Test)

The investigation of anti-inflammatory screening data reveals that all the tested compounds 6a-j have shown moderate to excellent anti-inflammatory activity. The compound no. 6b, 6d, 6f, 6h, 6i and 6j have shown promising activity. The good activity is attributed to the presence of pharmacologically active group such as tri methoxy phenyl, di methoxy phenyl, methoxy phenyl, furyl, N, N-dimethyl amino phenyl and hydroxy methyl phenyl. All these are electron- donor derivatives, were designed and synthesized and have shown good anti-inflammatory activity. The compound no. 6c having deactivating group exhibited lowest activity after 5hrs.

CONCLUSION:

In summary, we have developed a general and highly efficient ultrasound assisted procedure for the synthesis of 4-(3,5-diaryl substituted)-4,5-dihydro-1H-pyrazol-1-yl ) benzene sulfonamide derivatives. Particularly valuable features of this method include excellent yields and straightforward procedure, which expand the application of ultrasonic irradiation in the synthesis of heterocyclic compound, pyrazoline derivatives. Most of these compounds have exhibited significant anti-inflammatory activity. All the synthesized compounds were evaluated for the toxicity study. These compounds may serve as a lead compound for the search of more powerful selective anti-inflammatory agents.

ACKNOWLEDGEMENTS:

Authors are grateful to the Chairman, Maulana Azad Education Trust and the Principal Dr. M. H. Dehghan, Y.B Chavan College of Pharmacy, Aurangabad for encouragement and support. The authors wish to express their gratitude to Dr. H.M. Sampath Kumar, Chairman, Synthetic Chemistry and Biology Division, RRL, Jammu for their cooperation and Prof. Shashikant Pattan, KLE’s College of Pharmacy, Belgaum for his assistance during Pharmacological screening.

REFERENCES:

1. Polevoi LG. Tr Nauchn Konf Aspir Ordin, 1-yi (Peruyi) Mosk Med Inst, Moscow, Chem Abstr 159 (65): 1996:9147d.

2. Batulin YM. Anticonvulsant action of some derivatives of pyrazole. Farmakol Toksikol, 31:533. Chemical Abstract 70: 1969:2236a

3. Parmar SS. Pandey BR. Dwivedi C. Harbinson RD. Anticonvulsant activity and monoamine oxidase inhibitory properties of 1,3,5-trisubstituted pyrazolines. Journal of Pharmaceutical Science. 63:1974: 1152.

4. Soni N. Pande K. Kalsi R. and Barthwal JP. Inhibition of rat brain monoamine oxidase and succinic dehydrogenase by anticonvulsant pyrazolines. Res Commun Chem Pathol Pharmacol 56:1987:129.

5. Turan-Zitouni G. Chevallet P. Kilic FS. and Erol K. Synthesis of some thiazolyl- pyrazoline derivatives and preliminary investigation of their hypotensive activity. European Journal of Medicinal Chemistry 35:2000:635.

6. Prasad RY. Lakshmana Rao A. Prasoona K. Murali K. and Ravi Kumar P. Synthesis and antidepressant activity of some 1,3,5- triphenyl-2-prazolines and 3-(2"-hydroxynaphthalen-1"-yl)- 1,5-diphenyl-2-pyrazolines. Bioorganic Medicinal Chemistry letters 15:2005:5030.

7. Powers DG. Casebier DS. Fokas D.and Ryan WJ. Automated parallel synthesis of chalcone-based screening libraries. Tetrahedron 54:1998: 4085.

8. Luche JL. Synthetic Organic Sonochemistry, Plenum Press, New York 1998.

9. Li JT. Han JF. and Yang JH. Ultrasound Sonochemistry 10:2003: 199.

10. Mcnulty J. and Steere JA. and Wolf S. Tetrahedron Letters 39:1998: 8013.

11. Martings MAP. Pereira CMP and Cunico W. Ultrasound Sonochemistry13:2006:364.

12. Ji SJ. and Wang SY. Ultrasound Sonochemistry 12:2005: 339.

13. ZL. Shen, Wang SY. Zeng XF, Tetrahedron 61:2005: 10552.

14. Winter CA. Risley EA. Nus GN. Carrageenin-induced edema in hind paws of the rat as an assay for anti inflammatory drugs. Proc Soc Experimental Biology 111:1962: 544-547.

Received on 03.09.2011 Modified on 16.09.2011

Asian J. Research Chem. 4(11): Nov., 2011; Page 1712-1716