Synthesis and Biological Evaluation of the Pyrazole Class
Letters in Organic Chemistry, 2009, Vol. 6, No. 4
287
3.12 %H, 14.78 %N; IR, ꢀ cm-1: 3400 (OH) ,3250 (NH),
cellular infiltrate. In one group of rats (n=6), sterile saline
(0.9% w/ v; 2 ml) was injected into the air pouch instead of
carrageenan.
1
1660 (C=O), 1600 (C=N); H-NMR ꢁ: 7.52-8.31 (m, 13H,
aromatic+pyrazole C-5 H), 8.92 (s, 1H, CH=N), 9.85 (s, 1H,
NH), 12.18 (s, 1H, OH); MS, m/z (rel. abund. %): 463 (5.8,
M++2), 461 (13.8, M+), 332 (100), 194 (15.1), 142 (13.5),
110 (62.3).
Test Drugs
One hour prior to injection of carrageenan into the air
pouch, the rats (n=6 per group) were orally pretreated with
vehicle (1% carboxymethylcellulose) or one of the test drugs
at a dose of 10 mg/kg. Another series of experiments were
performed, in which the rats received Indomethacin
(10 mg/kg; n=6) 1 h prior to injection of carrageenan into the
air pouch.
N'-{[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]methylene}isonicotinohydrazide (15)
Yield 56%; M.p. 210-212oC; Calculated for
C22H16ClN5O. 2 H2O (437.88): 60.35 %C, 4.60 %H. Found:
60.71 %C, 4.28 %H; IR, ꢀ cm-1: 3200 (NH), 1670 (C=O),
1600 (C=N); 1H-NMR ꢁ: 7.37-8.96 (m, 14H, aroma-
tic+pyrazole C-5 H), 9.34 (s, 1H, CH=N), 9.92 (s, 1H, NH,
D2O exchangeable); MS, m/z (rel. abund. %): 403, (6.2,
M++2), 401 (15, M+), 279 (100), 106 (32.8), 77 (83.1).
Statistical Analysis
All data are expressed as the mean ± SD. Comparisons of
tested drugs versus Carrageenan-treated group were made by
unpaired student t-test.
N'-{[3-(4-Chlorophenyl)-1-(4-nitrophenyl)-1H-pyrazol-4-
yl]methylene}isonicotinohydrazide (16)
Modeling Studies
Yield 60%; M.p. > 300oC; Calculated for C22H15ClN6O3
(446.85): 59.13 %C, 3.38 %H, 18.81 %N. Found: 58.89 %C,
3.25 %H, 19.11 %N; IR, ꢀ cm-1: 3250 (NH), 1668 (C=O),
1600 (C=N); 1H-NMR ꢁ: 7.57-8.90 (m, 13H, aroma-
tic+pyrazole C-5 H), 9.36 (s, 1H, CH=N), 9.95 (s, 1H, NH,
D2O exchangeable).
Computer-assisted simulated docking experiments were
carried out under an MMFF94X force field in Cox-2
structure (PDB ID: 1CX2) using Chemical Computing
Group's Molecular Operating Environment (MOE-dock
2006) software, Montréal, Canada.
Preparation of 4-{N'-[3-(4-chlorophenyl)-1-phenyl-1H-
pyrazol-4-ylmethylene]hydrazino}benzenesulfonamide (17)
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Carrageenan-Air Pouch Model
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Materials and Methods
An air pouch was induced by subcutaneous injection of
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