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1007/s11094-017-1654-8
Pharmaceutical Chemistry Journal, Vol. 51, No. 7, October, 2017 (Russian Original Vol. 51, No. 7, July, 2017)
558
0091-150X/17/5107-0558 © 2017 Springer Science+Business Media New York
Synthesis and Anti-Inflammatory Activity 559
% Edema inhibition = 100 – (Vtest/Vcontrol) ´ 100. into 2-chlorobenzoic acid 2 by oxidation with potassium per-
manganate by following literature method. 2-Chlorobenz-
The results were expressed as percentage inhibition of ohydrazide 3 was obtained by refluxing 2-chlorobenzoic acid
paw edema relative to the untreated control group. The re- 2 with hydrazine hydrate in methanol. Compound 3 on reac-
sults of anti-inflammatory testing are given in Table 3. tion with potassium thiocyanate yielded corresponding
{(2-chlorobenzoyl)amino}thiourea 4 in good yield. The
RESULTS AND DISCUSSION 5-(2-chlorophenyl)-4H-1,2,4-triazole-3-thiol 5 was synthe-
sized by cyclization in the presence of base. 2-Bromo-1-
Chemistry (substituted phenyl)ethanones 6 were prepared by following
A novel series of 2-{[5-(2-chlorophenyl)-4H-1,2,4-tri- literature method.
azol-3-yl]sulfanyl}-1-(substituted phenyl)ethanone 7a – 7l Finally, 5-(2-chlorophenyl)-4H-1,2,4-triazole-3-thiol 5
were synthesized as shown in Scheme 1 by the reaction be- was treated with 2-bromo-1-(substituted phenyl)ethanone
tween 5-(2-chlorophenyl)-4H-1,2,4-triazole-3-thiol 5 and (6a – 6l) in the presence of base in ethanol medium to obtain
2-bromo-1-(substituted phenyl)ethanones 6a – 6l. The start- the corresponding 2-{[5-(2-chlorophenyl)-4H-1,2,4-triazol-
ing material 1-(2-chlorophenyl)ethanone 1 was converted 3-yl]sulfanyl}-1-(substituted phenyl)ethanone (7a – 7l).
Control 10 mg/kg 0.188 ± 0.0098 0.348 ± 0.0098 0.598 ± 0.0098 0.658 ± 0.0098 – – – –
Indomethacin 1.5 0.101 ± 0.0098 0.16 ± 0.0063 0.221 ± 0.0040 0.275 ± 0.0054 46.01** 54.06** 62.95** 58.22**
7a 50 0.128 ± 0.0040 0.231 ± 0.0040 0.396 ± 0.0081 0.468 ± 0.0040 31.85 33.49 33.70 28.86
7b 50 0.161 ± 0.0098 0.218 ± 0.0075 0.331 ± 0.0075 0.418 ± 0.0075 14.15** 37.32** 44.56** 36.45**
7c 50 0.171 ± 0.0160 0.318 ± 0.0204 0.548 ± 0.0040 0.641 ± 0.0204 8.84 8.61 8.356 2.53
7d 50 0.156 ± 0.0051 0.260 ± 0.0063 0.4 ± 0.0063 0.53 ± 0.0063 16.81 25.35 33.14 19.49
7e 50 0.158 ± 0.0098 0.278 ± 0.0040 0.418 ± 0.0040 0.551 ± 0.0040 15.92 20.09 30.08 16.20
7f 50 0.175 ± 0.0054 0.295 ± 0.0083 0.445 ± 0.0054 0.5 ± 0.0063 7.07 15.31 25.62 24.05
7g 50 0.153 ± 0.0051 0.248 ± 0.0040 0.346 ± 0.0051 0.456 ± 0.0051 18.58** 28.70** 42.06** 30.63**
7h 50 0.150 ± 0.0089 0.258 ± 0.0098 0.338 ± 0.0032 0.441 ± 0.0036 20.35** 25.83** 43.39** 32.93**
7i 50 0.175 ± 0.0083 0.315 ± 0.0083 0.558 ± 0.0116 0.643 ± 0.0081 7.07 9.56 6.68 2.27
7j 50 0.148 ± 0.0040 0.228 ± 0.0040 0.356 ± 0.0081 0.476 ± 0.0081 21.23** 34.44** 40.38** 27.59**
7k 50 0.150 ± 0.0020 0.230 ± 0.0020 0.340 ± 0.0020 0.401 ± 0.0036 19.91** 33.73** 43.03** 39.01**
7l 50 0.140 ± 0.0012 0.200 ± 0.0016 0.290 ± 0.0012 0.371 ± 0.0024 25.39** 42.39** 51.44** 43.64**
a
Values are presented as mean ± S. E. M (n = 6); data were analyzed by one-way ANOVA followed by Dunnett’s multiple comparison tests.
** p < 0.01 compared to control group.
Flash chromatography was used for purification of synthe- of standard drug indomethacin. Compounds 7a, 7c, 7d, 7e,
sized compound using a mixture of ethyl acetate and hexane 7f, 7i showed lesser degree of activity.
(1 : 1) as eluent. The flash chromatograph of 1-(4-fluorophe-
nyl)-2-{[5-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl]sulfanyl}e CONCLUSION
thanone 7l is shown in Fig. 1. The IR spectra of 2-{[5-(2-
chlorophenyl)-4H-1,2,4-triazol-3-yl]sulfanyl}-1-(substituted We have synthesized a novel series of 2-{[5-(2-chloro-
phenyl)ethanones 7a – 7l showed in each case stretching
phenyl)-4H-1,2,4-triazol-3-yl]sulfanyl}-1-(substituted phe-
bands of NH, Ar-H and CH2 in the regions of 3500 – 3200,
3031 – 3097, and 2985.60 – 2833.24 cm–1, respectively. The nyl) ethanones 7a – 7l and studied their anti-inflammatory
1
H-NMR spectra showed in each case the signal at activity. The obtained data show that compound 7l possesses
d = 7.94 – 7.17 ppm attributed to aromatic protons and at excellent anti-inflammatory activity. These results indicate
d = 4.62 – 4.57 ppm due to CH2 protons. The siglet appeared the necessity of fluoro substituent in the proposed system for
for NH of the triazole ring in the region of d = 10.77 – anti-inflammatory activity.
10.57 ppm, integrating one proton. The 13C NMR spectra
showed in each case the carbon of C=O, and triazole ring dis- REFERENCES
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