660 G. Chawla et al.
stretch); 1H NMR (DMSO-d6) δ (ppm): 7.30 (dd, 1H, J= 8.4
Hz, J= 8.1 Hz, 5-H), 7.48 (m, 1H, ArH), 7.92 (m, 2H, ArH),
7.98 (ddd, 1H, J= 5.1 Hz, J= 4.5 Hz, J= 2.1 Hz, 6-H), 8.01
(m, 2H, ArH) 8.16 (dd, 1H, J= 6.3 Hz, J= 2.1 Hz, 2-H); 13C
NMR (DMSO-d6) δ (ppm): 165.2 (C), 157.4 (C), 156.3 (C),
133.8 (C), 132.4 (C), 131.5 (C), 128.8 (C), 127.3 (2C), 126.1
(2C), 122.3 (C), 114.6 (C), 112.3 (C); MS: m/z 319 (M+);
Anal. Calcd for C14H8BrFN2O: C, 52.69; H, 2.53; N, 8.78;
Found C, 52.71; H, 2.54; N, 8.77%.
of phosphorous oxychloride (10 mL) for 3–5 h. e reac-
tion mixture was cooled to room temperature and poured
onto crushed ice with constant stirring. e mixture was
allowed to stand overnight and the solid thus separated
out was filtered, treated with 5% of dilute sodium hydrox-
ide solution, washed with water and recrystallised from
ethanol to give 7a–f.
3-(3-Bromo-4-fluorophenyl)-6-phenyl-1,2,
2-(3-Bromo-4-fluorophenyl)-5-(4-chlorophenyl)-
1,3,4-oxadiazole (4b)
2-(3-Bromo-4-fluorophenyl)-5-(4-fluorophenyl)-
1,3,4-oxadiazole (4c)
2-(3-Bromo-4-fluorophenyl)-5-(4-methylphenyl)-
1,3,4-oxadiazole (4d)
2-(3-Bromo-4-fluorophenyl)-5-(4-methoxyphenyl)-
1,3,4-oxadiazole (4e)
4-triazolo[3,4-b]-1,3,4-thiadiazole (7a)
FTIR (KBr pellet) cm−1: 3039 (aromatic C-H stretch); 1704
(C = N stretch); 1550, 1527, 1442 (C = C ring stretch); 1384
(N = C-S); 1292 (N-N = C); 1053 (C-F stretch); 563 (C-Br
stretch); 1H NMR (DMSO-d6) δ (ppm): 7.18 (dd, 1H, J= 8.7
Hz, J= 8.1 Hz, 5-H), 7.48 (m, 1H, ArH), 7.89 (m, 2H, ArH),
7.97 (ddd, 1H, J = 4.8 Hz, J= 4.5 Hz, J= 1.8 Hz, 6-H), 8.01
(m, 2H, ArH) 8.16 (dd, 1H, J= 6.9 Hz, J= 2.1 Hz, 2-H); 13C
NMR (DMSO-d6) δ (ppm): 164.2 (C), 160.7 (C), 157.1 (C),
154.3 (C), 134.3 (C), 132.6 (C), 131.4 (C), 128.3 (C), 126.8
(2C), 126.2 (2C), 116.3 (C), 113.8 (C), 112.4 (C); MS: m/z
375 (M+); Anal. Calcd for C15H8BrFN4S: C, 48.01; H, 2.15;
N, 14.93; Found C, 47.96; H, 2.15; N, 14.96%.
2-(3-Bromo-4-fluorophenyl)-5-(1-naphthylmethyl)-
1,3,4-oxadiazole (4f)
Synthesis of potassium salt of 3-bromo-
4-fluorobenzohydrazide (5)
A mixture of compound 3 (2.33 g, 0.01 mol), carbon disul-
fide (0.9 mL, 0.015 mol) and potassium hydroxide (0.84 g,
0.015 mol) in absolute ethanol (50 mL) was refluxed for
14 h. It was cooled to room temperature and diluted with
dry ether (25 mL). e solid so obtained was filtered,
washed with ether and vacuum dried at 65°C. e salt so
obtained was used as such for next step. Yield (67%).
3-(3-Bromo-4-fluorophenyl)-6-(4-chlorophenyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (7b)
3-(3-Bromo-4-fluorophenyl)-6-(4-fluorophenyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (7c)
3-(3-Bromo-4-fluorophenyl)-6-(4-methylphenyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (7d)
3-(3-Bromo-4-fluorophenyl)-6-(4-methoxyphenyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (7e)
Synthesis of 4-amino-5-(3-bromo-4-fluorophenyl)-
4H-1,2,4-triazole-3-thiol (6)
3-(3-Bromo-4-fluorophenyl)-6-(1-naphthylmethyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (7f)
A mixture of compound 5 (3.35 g, 0.01 mol), hydrazine
hydrate (1.0 mL, 0.02 mol) and water (15 mL) was refluxed
for 2 h. e contents turned green, hydrogen sulphide gas
was evolved and a homogenous mixture was obtained.
e contents were diluted with cold water (100 mL) and
acidified with hydrochloric acid; a white solid so obtained
was filtered, washed with cold water and recrystallised
from aqueous ethanol to give compound 6. Yield (65%);
m. p. 138°C–140°C.
Animals
Adult Wistar albino rats of either sex, weighing between
160 and 200 g were used for anti-inflammatory, ulcero-
genic and lipid peroxidation activities, whereas Swiss
albino mice of either sex, weighing between 18 and 25 g
were used to evaluate analgesic activity. e animals were
randomly distributed into groups at the beginning of all
the experiments. In each group six animals were kept. e
animals were allowed food and water ad libitum except
during the experiments. All the test compounds and the
reference drug were administered orally, suspended
in 1% carboxymethylcellulose (CMC) with one drop of
twin-80 solution wherever required. e experimental
protocol was approved by the animal ethics committee
of Jamia Hamdard.
FTIR (KBr pellet) cm−1: 3417 (N-H stretch); 3078 (aro-
maticC-Hstretch);2673(S-Hstretch)1685(C = Nstretch);
1539, 1508, 1427 (C = C ring stretch); 1292 (N-N = C); 1049
1
(C-F stretch); 497 (C-Br stretch); H NMR (DMSO-d6) δ
(ppm): 2.51 (s, 1H, S-H), 3.82 (s, 2H, NH2), 7.04 (dd, J= 8.4
Hz, J= 7.8 Hz, 1H, 5-H), 7.91 (ddd, 1H, J= 5.1 Hz, J= 4.2 Hz,
J= 1.8 Hz, 6-H), 8.14 (dd, 1H, J= 6.6 Hz, J= 1.8 Hz, 2-H); 13
C
NMR (DMSO-d6) δ (ppm): 165.7 (C), 160.4 (C), 158.3 (C),
136.1 (C), 134.3 (C), 126.4 (C), 118.1 (C), 112.3 (C); MS:
m/z 288 (M+); Anal. Calcd for C8H6BrFN4S: C, 33.23; H,
2.09; N, 19.38; Found C, 33.29; H, 2.09; N, 19.36%.
Anti-inflammatory activity
Anti-inflammatory activity was evaluated by carra-
geenan-induced hind paw oedema method32. Into the
subplantar region of the right hind paw of each rat,
0.1 mL of 1% carrageenan solution in saline was injected
subcutaneously, 1 h after administration of the test
compounds and standard drug. Control group received
only solution of 10 mL/kg 1% CMC with one drop of
twin-80. Standard drug ibuprofen was administered
General method for the synthesis of 3-(3-bromo-
4-fluorophenyl)-6-substituted-1,2,4-triazolo[3,4-b]-
1,3,4-thiadiazoles (7a–f)
Compound 6 (0.29 g, 0.001 mol) was refluxed with equi-
molar quantity of appropriate aromatic acid in presence
Journal of Enzyme Inhibition and Medicinal Chemistry