Synthesis of some novel 3-Alkyl/aryl-6-((1H-benzo[d][1,2,3]triazol-1-yl) methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

Article abstract of DOI:10.1002/jhet.178

(Chemical Equation Presented) A series of 3-alkyl/aryl substituted-6-((1H- benzo[d][1,2,3]triazol-1-yl)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles 4a-m are prepared by the condensation of 3-alkyl/aryl substituted-4-amino-5- mercapto-1,2,4-triazoles 2a-m with benzotriazole-1-yl acetic acid 3 through a single step reaction. The structures of all newly synthesized compounds are established on the basis of their IR, ¹H NMR, and elemental analyses data. Two selected compounds 4l and 4m are investigated for their analgesic and anti-inflammatory activities; they showed weak anti-inflammatory activity and no analgesic activity.

Full text of DOI:10.1002/jhet.178

September 2010
Synthesis of Some Novel 3-Alkyl/aryl-6-((1H-
benzo[d][1,2,3]triazol-1-yl)methyl)-[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazoles
1225
Xiqing Chen,a Chenjiang Liu,a,b* Jide Wang,a,b and Yanping Lia
aKey Laboratory of Oil and Gas Fine Chemicals, Ministry of Education, School of Chemistry and
Chemical Engineering, Xinjiang University, Urumqi 830046, People’s Republic of China
bSchool of Sciences, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
*E-mail: pxylcj@126.com
Received August 23, 2008
DOI 10.1002/jhet.178
Published online 13 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
A series of 3-alkyl/aryl substituted-6-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-[1,2,4]triazolo[3,4-b][1,
3,4]thiadizoles 4a–m are prepared by the condensation of 3-alkyl/aryl substituted-4-amino-5-mercapto-
1,2,4-triazoles 2a–m with benzotriazole-1-yl acetic acid 3 through a single step reaction. The structures
of all newly synthesized compounds are established on the basis of their IR, 1H NMR, and elemental
analyses data. Two selected compounds 4l and 4m are investigated for their analgesic and anti-inflam-
matory activities; they showed weak anti-inflammatory activity and no analgesic activity.
J. Heterocyclic Chem., 47, 1225 (2010).
INTRODUCTION
active nitrogen and sulphur containing heterocycles,
here we report the reaction of 3-alkyl/aryl substituted-4-
amino-5-mercapto-1,2,4-triazoles 2a–m with benzotria-
zole-1-yl acetic acid 3 in the presence of phosphorous
oxychloride to give 3-alkyl/aryl-6-((1H-benzo[d][1,2,3]-
triazol-1-yl)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadi-
zoles 4a–m (Scheme 1). In view of the reported biologi-
cal activities of triazolo thiadiazoles, two selected com-
pounds 4l and 4m are studied for their anti-inflamma-
tory and analgesic activities.
1,2,4-Triazoles and their heterocyclic derivatives rep-
resent an interesting class of compounds possessing a
wide spectrum of biological activities, such as antifungal
[1], antibacterial [2], antihypertensive [3], antileishma-
nial [4], anti-inflammatory [5], antiviral [6] activities. A
large number of thiadiazole-containing ring system
exhibits antibacterial [7] and antituberculosis [8] proper-
ties. Moreover, a survey of literature reveal that
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole rings received
much attention during recent years on account of their
prominent utilization as antifungal [9], anti-inflamma-
tory [10,11], antiviral, analgesic [12], anthelmintic [13],
anti-HIV-1 [14], and antibacterial agents [15]. A triazolo
thiadiazole system may be viewed as a cyclic analogue
of two very important components thiosemicarbazide
[16] and biguanide [17], which often display diverse
biological activities. On the other hand, benzotriazole
derivatives are of wide interest because of their diverse
biological activity and potential clinical applications
such as anti-inflammatory, antiviral, inactivator of
Severe acute respiratory syndrome (SARS) protease and
so on [18]. Therefore, it is envisaged that chemical enti-
ties with both [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
and benzotriazole would generate new interesting bio-
logical activities. In continuation of our ongoing
research program aimed at developing new biologically
RESULTS AND DISCUSSION
The reaction sequences employed for synthesis of title
compounds are shown in Scheme 1. The 3-alkyl-4-amino-5-
mercapto-1,2,4-triazoles 2a-f are synthesized by reacting
alkyl acid with thiocarbohydrazide [19]. The required aro-
matic hydrazides are prepared by esterification of aromatic
acid 1g-m followed by treatment with hydrazine hydrate in
absolute ethanol. The aromatic hydrazides are allowed to
react with carbon disulphide in the presence of potassium
hydroxide in ethanol to afford the corresponding intermedi-
ate potassium dithiocarbazinate. This salt undergoes ring
closure with an excess of 80% hydrazine hydrate to give 4-
amino-3-aryl-5-mercapto-1,2,4-triazoles 2g-m [20]. Benzo-
triazole-1-yl acetic acid 3 is prepared by treating benzotria-
zole with chloroacetic acid in sodium hydroxide solution
C
V
2010 HeteroCorporation

1226
X. Chen, C. Liu, J. Wang, and Y. Li
Vol 47
Scheme 1
Figure 1. Benzotriazole-1-yl acetic acid.
The structure assignments to new compounds 4a–m
are based on their elemental analyses and spectral data
1
(IR, H NMR). The IR spectra of the cyclized products
[21]. Condensation of 3-alkyl/aryl substituted-4-amino-5-
mercapto-1,2,4-triazoles 2a–m with benzotriazole-1-yl ace-
tic acid 3 in presence of boiling phosphorous oxychloride
yield 3-alkyl/aryl substituted-6-((1H-benzo[d][1,2,3]triazol-
1-yl)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles 4a–m
in 53–98% yields. Phosphorous oxychloride is necessary for
this condensation, which activate the carbonyl group of
acids and increase its electrophilicity to enhance the addition
of 1,2,4-triazoles to the target compounds.
4a–m show a characteristic absorption at 1445–1592
cmꢀ1 attributed to benzene ring of benzotriazole stretch-
ing. The band in the range of 1610–1614 cmꢀ1 indicate
1
the absorption of C¼¼N. In the H NMR spectra of com-
pounds 4a-m, the absorption bands characteristic of the
ACO2H and ANH2 groups are absent, thereby indicat-
ing the involvement of the amino group of triazole and
the carboxylic group of benzotriazole-1-yl acetic acid in
the condensation reaction. Moreover, we discover CH2
resonance appear singlets at 6.08–6.79 ppm. Thus, it is
further confirmed the involvement of these functional
groups in the cyclization of triazoles to triazolo
thiadiazoles.
The structural elucidation of 3 is completed by analy-
3
sis of gHSQC and gHMBC data. We can see that JH7-
(Fig. 1). In addition, we get the single crystal of com-
C6
pound 3. So compound 3 is benzotriazol-1-yl-acetic acid
but not benzotriazol-2-yl-acetic acid.
The inhibition ratio of compounds 4l and 4m are 8
and 22%, they show weak anti-inflammatory activity
(Table 1). 4l and 4m are further tested for their analge-
sic activity; unfortunately the results are not very good,
as they show no analgesic activity (Table 2).
Table 1
Anti-inflammatory activity tests.
Inhibition ratio
4l
4m
8%
22%
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
Synthesis of Some Novel 3-Alkyl/aryl-6-[(1H-benzo[d][1,2,3]triazol-1-yl)
methyl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
1227
Table 2
Table 4
Analgesic activity tests.
The fractional coordinates and mean temperature factors with
estimated standard deviations.
20 min
40 min
60 min
x
y
z
Ueq
4l
4m
0
10.07%
0
0
12.76%
0
O1
O2
N1
N2
N3
C1
C2
0.39231 (10) 0.5275 (3) 0.16463 (9) 0.0530 (4)
0.26751 (15) 0.2779 (4) 0.19909 (10) 0.0896 (6)
0.34289 (11) 0.5060 (3) 0.38224 (9)
0.38836 (12) 0.3101 (4) 0.45424 (9)
0.32632 (12) 0.2965 (4) 0.50331 (10) 0.0484 (4)
0.23907 (14) 0.4873 (4) 0.46255 (11) 0.0435 (4)
0.15091 (16) 0.5552 (5) 0.48832 (15) 0.0580 (5)
0.0421 (4)
0.0472 (4)
EXPERIMENTAL
The IR spectra are obtained as potassium bromide pellets
with a FTS-40 spectrometer (BIO-RAD, U.S.A). The one-
dimensional (1H) and two-dimensional (gHSQC, gHMBC)
NMR spectra are obtained on a Varian Inova-400 (400 MHz)
spectrometer using CDCl3 or DMSO-d6 as solvent (shown in
detail in data part) and tetramethylsilane as an internal stand-
ard, chemical shifts are given in ppm. Elemental analyses (C,
H, N) are performed on a Perkin-Elmer Analyzer 2400. Melt-
ing points are determined using a Bu¨chi B-540 instrument and
are uncorrected (Tables 3–6).
H2B 0.1442
C3 0.07567 (18) 0.7523 (5) 0.43111 (17) 0.0670 (6)
H3B 0.0155 0.8006 0.4455 0.080
C4 0.08574 (16) 0.8857 (5) 0.35093 (16) 0.0635 (6)
H4A 0.0321 1.0196 0.3141 0.076
C5 0.17192 (15) 0.8249 (4) 0.32535 (13) 0.0525 (5)
H5A 0.1788 0.9136 0.2725 0.063
0.4699
0.5418
0.070
C6
C7
0.24864 (13) 0.6217 (4) 0.38365 (11) 0.0404 (4)
0.39868 (14) 0.5775 (5) 0.31981 (11) 0.0472 (4)
H7A 0.4739
H7B 0.4009
0.5066
0.7922
0.3489
0.3136
0.057
0.057
Table 3
C8
H1
0.34422 (15) 0.4428 (4) 0.22160 (12) 0.0456 (4)
0.360 (2) 0.419 (6) 0.1049 (19) 0.094 (8)
Crystal data and summary of data collection and structure refinment.
Compound
C8H7N3O2
Colorless/chip
177.17
Color/shape
Formula weight
Temperature (ꢁC)
Crystal system
Space group
Benzotriazole-1-yl acetic acid (3). Add 4.8 g (40 mmol)
benzotriazole, 3.8 g (40 mmol) chloroacetic acid, 3.2 g (80
mmol) sodium hydroxide, and 100 mL water into a round bot-
tom flask, reflux slowly for 3 h, filter immediately after reflux.
The filtrate is cooled at room temperature and acidified with
dilute hydrochloric acid till no deposit appear. It is filtered and
washed thoroughly with cold water, dried, and recrystallized
293(2)
Monoclinic
P2(1)/c
Cell constants
˚
a (A)
˚
13.234(2)
4.4889(7)
b (A)
˚
c (A)
15.142(2)
90.00
113.135(3)
90.00
827.2(2)
from butanol, Yield 78%, mp 216–218ꢁ.
a (ꢁ)
b (ꢁ)
c (ꢁ)
3
gHMBC: (DMSO-d6): JH3-C1
,
,
3JH5-C1
, , ,
3JH4-C2 3JH5-C3
3JH2-C4
,
3JH3-C5
,
3JH4-C6
,
3JH2-C6
3JH7-C6. Anal. Calcd. for
3
˚
Volume (A )
C8H7N3O2 (177.16): C, 54.24; H, 3.98; N, 23.72. found: C,
54.43; H, 3.92; N, 23.61.
Formula units/units cell
Dcalc (g cmꢀ3
F (000)
4
1.423
)
General procedure for preparation synthesis of 3-alkyl/
aryl substituted-6-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (4a–m). An equimolar
mixture of respective triazole 2a–m (1 mmol) and benzotria-
zole-1-acetic acid (1 mmol) in phosphorus oxychlorid (8 mL)
are refluxed for 7 h. Excess of phosphorus oxychlorid is
removed under reduced pressure. The resulting reaction mass
is cooled and gradually poured onto crushed ice with stirring,
the result mixture is allowed to stand overnight and the solid
separated out is filtered. Finally, the filter cake is washed thor-
oughly with water till the pH of the filtrate is raised to 7,
dried, and recrystallized from a mixture of DMF and ethanol.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-methyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4a). This compound was
obtained as white needle solid, 87% yield, mp 141–142ꢁ; IR
(KBr): 3090, 2986, 2933, 1608, 1592, 1536, 1494, 1464, 1290
;
cmꢀ1 1H NMR (CDCl3): d 2.75 (s, 3H), 6.13 (s, 2H), 7.45–
8.16 (m, 4H). Anal. Calcd. for C11H9N7S (271.30): C, 48.70;
H, 3.34; N, 36.14. Found: C, 48.82; H, 3.28; N, 36.27.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(trifluoromethyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4b). This compound was
obtained as white solid, 93% yield, mp 148–151ꢁ; IR (KBr):
;
3094, 2937, 1613, 1592, 1544, 1524, 1497, 1295 cmꢀ1 1H
368.0
0.106
Absorption coefficient, m lꢀ1
Diffractometer/Scan
Radiation, graphite
Monochromator Mo Ka
Reflections for cell
measurement
Enraf-Noius CAD4, x/2y
k ¼ 0.71073 A
˚
27.48, 3.35–27.48
and y range (ꢁ)
Index ranges
ꢀ17 ꢂ h ꢂ 17; ꢀ5 ꢂ k ꢂ 5;
ꢀ19 ꢂ l ꢂ 19
Reflection observed
[1 > 2r(I)]
Maximum
value of y(ꢁ)
Computing
1775 [R(int) ¼ 0.0249]
27.48
Data collection CAD4
Cell refinement CAD4
Data reduction PCSDP
SHELXL-97
SHELXL-97
1775/0/123
Structure solution
Structure refinement
Data/restrains/parameters
Goodness-of-fit on F2
Final R indices
1.071
R1 ¼ 0.0406; wR2 ¼ 0.1115
Largest diff. peaꢀk3
0.208 and ꢀ0.186
˚
and hole (e A
)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1228
X. Chen, C. Liu, J. Wang, and Y. Li
Vol 47
Table 5
(KBr): 3072, 2954, 1613, 1581, 1568, 1475, 1459, 1274 cmꢀ1
;
1H NMR (CDCl3): d 6.25 (s, 2H), 7.49–8.86 (m, 8H). Anal.
Calcd. for C15H10N8S (334.36): C, 53.88; H, 3.01; N, 33.51.
Found: C, 53.76; H, 3.07; N, 33.62.
Selected bond lengths.
O1
C8
1.3136 (19)
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(pyridin-3-yl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h). This compound
was obtained as brown solid, 59% yield, mp 149–152ꢁ; IR
O1
O2
N1
N1
N1
N2
N3
C1
C1
C2
C2
C3
C3
C4
C4
C5
C5
C7
C7
C7
H1
C8
0.97 (3)
1.193 (2)
1.3448 (19)
1.359 (2)
1.4457 (19)
1.3074 (19)
1.374 (2)
1.388 (2)
1.402 (2)
1.359 (3)
0.9300
N2
C6
(KBr): 3071, 2938, 1612, 1586, 1566, 1471, 1464, 1268 cmꢀ1
;
1H NMR (DMSO-d6): d 6.36 (s, 2H), 7.53–8.88 (m, 8H).
Anal. Calcd. for C15H10N8S (334.36): C, 53.88; H, 3.01; N,
33.51. Found: C, 54.01; H, 3.08; N, 33.69.
C7
N3
C1
C6
C2
C3
H2B
C4
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-phenyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4i). This compound was
obtained as brown solid, 98% yield, mp 205–207ꢁ; IR (KBr):
;
3084, 2953, 1614, 1585, 1550, 1471, 1463, 1265 cmꢀ1 1H
NMR (DMSO-d6): d 6.63 (s, 2H), 7.49–8.16 (m, 9H). Anal.
Calcd. for C16H11N7S (333.37): C, 57.65; H, 3.33; N, 29.41.
Found: C, 57.81; H, 3.27; N, 29.27.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(4-nitrophenyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4j). This compound was
obtained as muddy color solid, 98% yield, mp 172–175ꢁ; IR
1.406 (3)
0.9300
1.368 (3)
0.9300
1.392 (2)
0.9300
1.501 (2)
0.9700
0.9700
H3B
C5
H4A
C6
H5A
C8
(KBr): 3089, 2973, 1611, 1582, 1574, 1462, 1453, 1283 cmꢀ1
;
H7A
H7B
1H NMR (DMSO-d6): d 6.75 (s, 2H), 7.55–8.25 (m, 8H).
Anal. Calcd. for C16H10N8O2S (378.37): C, 50.79; H, 2.66; N,
29.61. Found: C, 50.93; H, 2.71; N, 29.47.
NMR (CDCl3): d 6.21 (s, 2H), 7.47–8.17 (m, 4H). Anal.
Calcd. for C11H6N7F3S (325.27): C, 40.62; H, 1.86; N, 30.14.
Found: C, 40.79; H, 1.91; N, 30.32.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-isopropyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4c). This compound was
obtained as brown solid, 66% yield, mp 238–240ꢁ; IR (KBr):
3077, 2962, 1612, 1565, 1549, 1467, 1445, 1260 cmꢀ1 1H
;
Table 6
Selected bond angles (°).
C8
N2
N2
C6
N3
N2
N3
N3
C6
C3
C3
C1
C2
C2
C4
C5
C5
C3
C4
C4
C6
N1
N1
C1
N1
N1
C8
N1
C8
H7A
O2
O2
O1
O1
N1
N1
N1
N2
N3
C1
C1
C1
C2
C2
C2
C3
C3
C3
C4
C4
C4
C5
C5
C5
C6
C6
C6
C7
C7
C7
C7
C7
C7
C8
C8
C8
H1
C6
108.6 (15)
110.99 (13)
119.63 (14)
129.29 (15)
108.07 (14)
108.69 (14)
108.22 (14)
130.92 (17)
120.85 (18)
116.46 (19)
121.8
NMR (DMSO-d6): d 1.23 (d, 6H), 2.67 (m, 1H), 6.50 (s, 2H),
7.45–8.10 (m, 4H). Anal. Calcd. for C13H13N7S (299.35): C,
52.16; H, 4.38; N, 32.75. Found: C, 52.27; H, 4.42; N, 32.58.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-propyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4d). This compound was
obtained as gray solid, 82% yield, mp 130–132ꢁ; IR (KBr):
C7
C7
N1
C1
C6
C2
C2
C1
3085, 2971, 1610, 1584, 1572, 1493, 1468, 1263 cmꢀ1 1H
;
NMR (DMSO-d6): d 1.21 (t, 3H), 1.86 (m, 2H), 2.42 (t, 2H),
6.53 (s, 2H), 7.43–8.12 (m, 4H). Anal. Calcd. for C13H13N7S
(299.35): C, 52.16; H, 4.38; N, 32.75. Found: C, 51.94; H,
4.33; N, 32.59.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-isobutyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4e). This compound was
obtained as light yellow solid, 58% yield, mp 129–131ꢁ; IR
(KBr): 3088, 2988, 2937, 1613, 1590, 1570, 1483, 1448, 1293
;
cmꢀ1 1H NMR (DMSO-d6): d 0.88 (d, 6H), 2.11 (m, 1H),
2.84 (d, 2H), 6.55 (s, 2H), 7.46–8.14 (m, 4H). Anal. Calcd. for
C14H15N7S (313.38): C, 53.66; H, 4.82; N, 31.29. Found: C,
53.83; H, 4.89; N, 31.38.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-pentyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4f). This compound was
obtained as pink solid, 94% yield, mp 105–108ꢁ; IR: 3080, 2991,
;
2939, 1611, 1585, 1567, 1484, 1455, 1298 cmꢀ1 1H NMR
H2B
H2B
C4
H3B
H3B
C3
121.8
122.24 (19)
118.9
118.9
122.1 (2)
118.9
118.9
115.62 (18)
122.2
122.2
H4A
H4A
C6
H5A
H5A
C1
C5
C5
104.02 (15)
133.28 (15)
122.70 (16)
112.86 (14)
109.0
C8
H7A
H7A
H7B
H7B
H7B
O1
109.0
109.0
(CDCl3): d 0.93 (t, 3H), 1.33–1.90 (m, 6H), 3.10 (t, 2H), 6.08 (s,
2H), 7.45–8.16 (m, 4H). Anal. Calcd. for C15H17N7S (327.41): C,
55.03; H, 5.23; N, 29.95. Found: C, 55.19; H, 5.19; N, 30.13.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(pyridin-4-yl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4g). This compound
was obtained as brown solid, 53% yield, mp 208–211ꢁ; IR
109.0
107.8
124.73 (17)
123.80 (15)
111.46 (15)
C7
C7
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
Synthesis of Some Novel 3-Alkyl/aryl-6-[(1H-benzo[d][1,2,3]triazol-1-yl)
methyl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
1229
animals and observe the reaction time of animals on the hot
plate at 20, 40, and 60 min after the compound administration.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(3-nitrophenyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4k). This compound
was obtained as light blue solid, 82% yield, mp 148–151ꢁ; IR
(KBr): 3084, 2970, 1614, 1578, 1563, 1471, 1458, 1263 cmꢀ1
;
Acknowledgments. We gratefully thank the National Natural
Science Foundation of China (No. 20662009) and Specialized
Research Fund for the Doctoral Program of Higher Education
(No. 20050755003) for their support.
1H NMR (DMSO-d6): d 6.79 (s, 2H), 7.61–8.22 (m, 8H).
Anal. Calcd. for C16H10N8O2S (378.37): C, 50.79; H, 2.66; N,
29.61. Found: C, 50.62; H, 2.59; N, 29.73.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-p-tolyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazole (4l). This compound was
obtained as white solid, 98% yield, mp 207–210ꢁ; IR (KBr):
3071, 2940, 1610, 1588, 1544, 1471, 1462, 1271 cmꢀ1 1H
;
REFERENCES AND NOTES
NMR (DMSO-d6): d 2.38 (s, 3H), 6.62 (s, 2H), 7.36–8.16(m,
8H). Anal. Calcd. C17H13N7S (347.40): C, 58.78; H, 3.77; N,
28.22. Found: C, 58.61; H, 3.83; N, 28.35.
6-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-3-(furan-2-yl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4m). This compound
was obtained as white solid, 64% yield, mp 189–192ꢁ; IR
[1] Heeres, J.; Backx, L. J. J Med Chem 1984, 27, 894.
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(KBr): 3082, 2963, 1612, 1587, 1550, 1482, 1448, 1282 cmꢀ1
;
1H NMR (DMSO-d6): d 6.62 (s, 2H), 6.76–8.15 (m, 7H).
Anal. Calcd. for C14H9N7OS (323.33): C, 52.01; H, 2.81; N,
30.32. Found: C, 52.22; H, 2.75; N, 30.45.
ˇ
[5] Labanauskas, L.; Udrenaite, E.; Gaidelis, P.; Brukstus, A.
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Anti-inflammatory activity. This activity is performed by
the following procedure of Winter et al. [22] on groups of six
animals each. A freshly prepared suspension of carrageen in
(1.0% w/v, 0.1 mL) is injected in the planter region of right
hind paw of each rat. One group is kept as control and the ani-
mals of the other group are pretreated with the test drugs sus-
pended in 1.0% CMC given orally 1 h before the carrageenin
treatment. The volume is measured before and after 4 h of car-
rageenin treatment with the help of pleythysmometer. The per-
cent anti-inflammatory activity is calculated according to the
formula given below:
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J Med Chem 2007, 42, 823.
%Anti-inflammatory activity ¼ ðVc ꢀ Vt=VcÞ ꢃ 100
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where Vt represents the mean increase in paw volume in rats
treated with test compounds and Vc represents the mean
increase in paw volume in control group of rats. Data are
expressed as mean ꢄ S.E.M., Student’s t-test is applied to
determine the significance of the difference between the con-
trol group and rats treated with the test compounds.
Analgesic activity. This activity is performed by Eddy’s hot
plate technique [23], Mice (Swiss strain) of either sex weigh-
ing between 25 and 35 g are used for the experiment. In this
method heat is used as a source of pain. Animals are individu-
ally placed on a hot plate, maintained at constant temperature
(55ꢁC) and the reaction of animals, such as paw licking or
jumping response (whichever appears first) is taken as the end
point. A cut-off time of 15 s is taken as maximum analgesic
response to avoid injury to the paws. The tested compounds
and diclofenac sodium (standard) at a dose of 30 mg/kg body
weight in 1% gum acacia are given as suspension orally to
[20] Reid, J. R.; Heindel, N. D. J Heterocycl Chem 1976, 13, 925.
[21] Li, Y. X.; Liu, F. A.; Liu, X. M. Acta Scientiarum Natural-
ium Universitatis Jilinensis 1992, 3, 122.
[22] Winter, C. A.; Riseny, E. A.; Nuss, G. W. Proc Soc Exp
Biol Med 1962, 111, 544.
[23] Eddy, N. B.; Leimbach, D. J. J Pharmacol Exp Ther 1953,
107, 385.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet