New 6-bromoimidazo[1,2-A]pyridine-2-carbohydrazide derivatives: Synthesis and anticonvulsant studies

Article abstract of DOI:10.1007/s00044-013-0887-7

In the present work, we report the facile synthesis and anticonvulsant study of new imidazo[1,2-A]pyridines carrying biologically active hydrazone functionality (3a-3e) and suitably substituted 1,2,4-triazole moieties (4, 5a-5d, 6, and 7a-7d). The newly synthesized intermediates and final compounds were characterized by various spectral techniques such as FTIR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis studies. The in vivo anticonvulsant study of the target compounds were carried out following maximal electroshock seizure and subcutaneous pentylene tetrazole methods, while their toxicity study was performed following rotarod method by taking 20, 40, and 100 mg/kg dose levels. Most of the new compounds displayed remarkable anticonvulsant properties at these doses. Particularly, compounds 3b and 4 carrying hydrogen bond donor groups, viz. hydroxyl and amine moieties respectively, exhibited complete protection against seizure and their results are comparable to that of standard drug diazepam. Further, the motor impairment study revealed that all the compounds are nontoxic upto 100 mg/kg.

Full text of DOI:10.1007/s00044-013-0887-7

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-013-0887-7
ORIGINAL RESEARCH
New 6-bromoimidazo[1,2-a]pyridine-2-carbohydrazide
derivatives: synthesis and anticonvulsant studies
•
Shrikanth Ulloora Ramakrishna Shabaraya
•
Airody Vasudeva Adhikari
Received: 11 April 2013 / Accepted: 5 December 2013
Ó Springer Science+Business Media New York 2013
Abstract In the present work, we report the facile syn-
thesis and anticonvulsant study of new imidazo[1,2-a]
pyridines carrying biologically active hydrazone function-
ality (3a–3e) and suitably substituted 1,2,4-triazole moie-
ties (4, 5a–5d, 6, and 7a–7d). The newly synthesized
intermediates and final compounds were characterized by
Introduction
Epilepsy is a heterogeneous mixture of disorders charac-
terized by neuronal hyperexcitability and hypersynchro-
nous neuronal firing, which affects about 1 % of the human
population (Zhang et al., 2012). Regrettably, around 90 %
epileptic patients are from developing countries. At pres-
ent, many antiepileptic drugs (AEDs) are available, but
such trivial drugs are able to control the seizure in only
about 60 % of patients or they can decrease the incidence
in only about 75 % of patients (Gupta et al., 2011). In this
context, many new generation of AEDs have been devel-
oped, which show improved therapeutic actions. But their
toxicity and adverse side effects limit their utility (Picot
et al., 2008; Naithani et al., 2010). Moreover, the mecha-
nism of action for many existing drugs is remaining mys-
tery and this significantly affects the development of new
anticonvulsants. The discovery of new safer AEDs with
proper mechanism of action may circumvent the short-
comings of current anticonvulsants. Due to the lack of
knowledge about mechanism of action for various AEDs,
structural modification approach appears to be an effective
route for the development of new therapeutic agents rather
than mechanism-driven design (Obniska et al., 2012).
Imidazo[1,2-a]pyridines are the important class of CNS
agents, acting as the potential sedatives, anticonvulsants,
anxiolytics, and hypnotics. They produce relatively less
side effects when compared to those of classical benzodi-
azepines and so, they are claimed to be the efficient sub-
stitutes for trivial drugs. Interestingly, the CNS activity of
various imidazo[1,2-a]pyridine-based drugs are found to be
dose dependant and so, they display different CNS activi-
ties at various doses. Important imidazo[1,2-a]pyridine
drugs such as Zolpidem, Alpidem, Saripidem etc. are act-
ing as the potential anticonvulsant agents against PTZ
1
various spectral techniques such as FTIR, H NMR, 13C
NMR, and mass spectral and elemental analysis studies.
The in vivo anticonvulsant study of the target compounds
were carried out following maximal electroshock seizure
and subcutaneous pentylene tetrazole methods, while their
toxicity study was performed following rotarod method by
taking 20, 40, and 100 mg/kg dose levels. Most of the new
compounds displayed remarkable anticonvulsant properties
at these doses. Particularly, compounds 3b and 4 carrying
hydrogen bond donor groups, viz. hydroxyl and amine
moieties respectively, exhibited complete protection
against seizure and their results are comparable to that of
standard drug diazepam. Further, the motor impairment
study revealed that all the compounds are nontoxic upto
100 mg/kg.
Keywords Imidazo[1,2-a]pyridine Á 1,2,4-Triazole Á
Hydrazone Á Anticonvulsant study Á Neurotoxicity
S. Ulloora Á A. V. Adhikari (&)
Department of Chemistry, National Institute of Technology
Karnataka, Surathkal, Mangalore 575 025, Karnataka, India
e-mail: avadhikari123@yahoo.co.in; avchem@nitk.ac.in
R. Shabaraya
Srinivas College of Pharmacy, Valachil, Mangalore, Karnataka,
India
123

Med Chem Res
induced seizures (Tomczuk et al., 1991) and particularly,
Zolpidem is found to be anticonvulsant active at smaller
doses (Vlainic and Pericic, 2010). Recently, we reported
significant anticonvulsant activity for new imidazo[1,2-a]
pyridines carrying aryl substituents at second position
(Ulloora et al., 2012). Encouraged by this and also, as a
part of our continued research on design and synthesis of
new antiepileptic agents, in this present work, it has been
thought of developing some new anticonvulsants derived
from 2-substituted imidazo[1,2-a]pyridines.
following appropriate synthetic routes. The reaction
sequence employed for the synthesis of target compounds
3a–3e, 5a–5d, and 7a–7d is given in Scheme 1. The newly
1
synthesized compounds were characterized by FTIR, H
NMR, 13C NMR, and mass spectrometry followed by
elemental analysis studies. Further, the new compounds
were screened for their in vivo anticonvulsant properties
following maximal electroshock seizure (MES) and sub-
cutaneous pentylene tetrazole (scPTZ) screening method-
ologies, followed by their Rotarod toxicity study.
During the last decade, the 1,2,4-triazole field has grown
rapidly, probably owing in part to the medicinal interest
which 1,2,4-triazoles command. Several aryl substituted
1,2,4-triazoles were shown to display variety of biological
properties. It is well-established that 1,2,4-triazole moiety
possesses greater affinity toward epileptic receptors and
thereby enhances the anticonvulsant property of its deriv-
atives (Dawood et al., 2006; Mokrab et al., 2007). The
presence of hydrogen bonding donor/acceptor groups on
the 1,2,4-triazole moiety and the hydrophobic aryl unit
attached to it, are the most probable reasons for their good
bio-efficacy (Deng et al., 2011). Active anticonvulsant
drugs like Alprazolam and Estazolam carry triazole moiety
as an important pharmacophore in their structure. More-
over, antiepileptic property of various triazole derivatives
were documented in many research articles (Guan et al.,
2010; Plech et al., 2012; Piao et al., 2011). In addition to
antiepileptic property, they were reported to possess many
other pharmacological applications such as antimicrobial
(Murthy et al., 2012), antiprotozoal (Durust et al., 2012),
anti-tubercular (Costa et al., 2006), anti-inflammatory
(Abdel-Megeed et al., 2009), and anticancer (Sztanke
et al., 2008) activities.
Results and discussion
Chemistry
The imidazo[1,2-a]pyridine-2-carboxylate derivative 1 was
synthesized following reported procedure (Herath et al.,
2010) by refluxing 5-bromo-2-aminopyridine with ethyl
bromopyruvate in ethanol medium. This solid ester product
was later reacted with hydrazine hydrate to attain active
scaffold hydrazide 2. The hydrazide 2 was reacted with
appropriate aromatic aldehydes in presence of a drop of
conc. sulfuric acid as a dehydrating agent, to get a set of
hydrazones 3a–3e. On the other hand, hydrazide 2 was
cyclized to 1,2,4-triazole 4, by stirring hydrazide 2 with
carbon disulfide and potassium hydroxide at room tem-
perature followed by reflux with hydrazine hydrate under
ethanol media for 6 h. The free amine group of 4 was
condensed with different aromatic aldehydes in presence of
acidic catalyst to get a set of Schiff bases 5a–5d. Similarly,
hydrazide 2 was refluxed with phenyl isothiocyanate under
ethanol medium to get thiosemicarbazide intermediate that
later cyclized to 4-phenyl-1,2,4-triazole-3-thiol derivative
6 by stirring with 2 N NaOH at 80 °C. Finally, the free
thiol group of 6 was alkylated with appropriate alkyl/ben-
zyl halides in the presence of potassium carbonate to afford
7a–7d. At the end, all these newly synthesized intermedi-
ates and target compounds were purified by recrystalliza-
tion or column chromatography technique.
To the best of our knowledge, the synthetic and bio-
logical strategy of heterocyclic hybrids containing imi-
dazo[1,2-a]pyridine and 1,2,4-triazole moieties in a single
organic framework is not reported in the literature. Against
this background, it has been contemplated to incorporate a
suitably substituted 1,2,4-triazole group at second position
of biologically active imidazo[1,2-a]pyridine core in our
new design, with the expectation of enhanced antiepileptic
activity for resulting hybrid molecules. In addition, several
heterocyclic hydrazone derivatives were shown to exhibit a
good anticonvulsant activity (Kulandasamy et al., 2009).
Hydrazone linkage possesses hydrogen bond donor, as well
as acceptor groups, which are found to enhance the anti-
epileptic property of resulting molecules, by being
involved in hydrogen bonding interactions with receptor
site (Dimmock et al., 2000). Keeping this in view, it has
been also planned to develop new imidazo[1,2-a]pyridines
carrying hydrazone pharmacophore at second position.
Accordingly, new derivatives of imidazo[1,2-a]pyridines
carrying hydrazone and 1,2,4-triazoles were synthesized
The structures of new derivatives were confirmed by
their FTIR, 1H NMR, 13C NMR, and mass spectral studies
followed by elemental analysis data. The cyclization of
5-bromo-2-aminopyridine into 6-bromoimidazo[1,2-a]pyr-
idine-2-carboxylate (1) was confirmed by their FTIR and
1H NMR spectral studies. In the FTIR spectrum of com-
pound 1, the peaks due to amine and ketonic groups of
starting materials, viz. 5-bromo-2-aminopyridine and ethyl
bromopyruvate, respectively disappeared, while a new
peak at 1,697 cm-1 corresponding to carboxylate group
appeared. Appearance of two singlets in its 1H NMR
spectrum at d 8.94 and 8.37 ppm, corresponding to two
aromatic protons present at C-5 and C-3 positions,
123

Med Chem Res
Scheme 1 Synthetic routes for
target compounds. a Ethanol,
80 °C, 6 h; b N2H4.H2O,
Br
Br
a
Br
+
NH2
COOEt
N
N
N
O
Ethanol, 80 °C, 6 h; c ArCHO,
Ethanol, H?, 80 °C, 6–8 h, d,
i CS2, KOH, Ethanol, 25 °C,
8 h; ii N2H4.H2O, 80 °C, 6 h;
e ArCHO, Ethanol, H?, 80 °C,
6–8 h; f i PhNCS, Ethanol,
70 °C, 8 h; ii 2 N NaOH, 80 °C,
4 h; g RBr, K2CO3, DMF,
60 °C, 6 h
COOEt
1
b
Br
Br
Br
d
c
Aryl
N
N
N
N
N
: Thiophen-2-yl
: 4-OH Ph
: 4-F Ph
: 4-Nitro Ph
: Vanilin
3a
3b
3c
3d
3e
N
NH
NH2
N
O
NH
O
N
N
H2N
2
N
Aryl
4
HS
3a-e
f
e
Br
Br
Br
N
N
g
N
N
N
N
N
N
N
N
N
N
N
N
N
N
S
HS
HS
R
R
7a-d
6
5a-d
R 4-Me
: R=4-OH;
5a
5b:
=
: R=Pr;
: R=Benzyl
7a
7c
7b
: R=4-Nitro;
: R=F
5c
5d
: R=4-MeO Benzyl;
: R=4-NO2 Benzyl
7d
respectively, also supported the proposed structure. These
two protons resonated at down field, because of the
inductive field effect offered by adjacent electronegative
nitrogen atom. Moreover, appearance of a quartet and a
triplet at d 3.98 and 0.96 ppm clearly confirms the presence
of ethyl carboxylate group. In the FTIR spectrum of 2, new
peaks at 3,448, 3,256, and 3,159 cm-1 have appeared
corresponding to hydrazidic NH and NH2 groups, respec-
tively. On the other hand, a downshift in the carbonyl
stretching frequency was observed from 1,697 to
1,677 cm-1, when ester was converted into hydrazide. The
1H NMR spectrum of compound 2 showed a new peak at d
9.89 ppm corresponding to CONH proton, while NH2 peak
appeared at d 4.28 ppm. The complete disappearance of
quartet and a triplet peak of ethyl carboxylate group of
compound 1 and appearance of two characteristic peaks
corresponding to NH and NH2 protons, clearly confirm the
conversion of 1–2. In the FTIR spectrum of 3a, the peak
due to NH2 group of hydrazide 2 has disappeared, while
peak due to NH stretching has shifted from 3,448 to
3,297 cm-1. Similarly, the carbonyl stretching peak has
shifted from 1,677 to 1,670 cm-1, upon coupling with
thiophene-2-aldehyde, which evidences the formation of
hydrazone 3a. In the same way, a down field shift was
observed in the 1H NMR spectrum of compound 3a for NH
peak, while a new prominent peak has appeared at d
8.55 ppm corresponding to vinylic proton of imine group,
which clearly confirms the proposed structure. This was
further evidenced by its mass spectral data, wherein a mass
peak of 350.7 (M?1) was observed which is in accordance
with its molecular formula C13H9BrN4OS.
The cyclization of hydrazide 2 into 4-amino-1,2,4-tria-
1
zole-3-thiol 4 was confirmed by its H NMR spectrum,
which showed characteristic peaks at d 13.88 and 5.91 ppm
corresponding to tautomeric NHCS and NH2 protons,
respectively. The appearance of peak at d 13.88 ppm due to
NH group clearly shows that the triazole ring might be
stable in the keto (thione) tautomeric form than thiol form.
1
In the H NMR spectrum of 5a, the amine peak of 4 at d
5.91 ppm has disappeared, while a new peak has appeared
at d 9.51 ppm that corresponds to CH=N proton, con-
firming the conversion of amine into imine. Appearance of
another new peak at d 10.41 ppm corresponding to phe-
nolic group further confirms the conversion. Synthesis of
4-phenyl-1,2,4-triazol-3-thiol derivative 6 was evidenced
by its 1H NMR spectrum, where peaks due to NH and NH2
123

Med Chem Res
M.P. (oC)
Table 1 Physical data of target compounds 3a–7d
Sample
R/Aryl
Molecular formula
C13H9BrN4OS
Mol. Wt. (g)
Yield (%)
3a
3b
3c
3d
3e
4
Thiophen-2-yl
4-Hydroxyphenyl
4-Fluorophenyl
4-Nitrophenyl
Vanilinyl
–
349.2
359.2
361.2
388.2
389.2
311.2
415.3
413.3
444.3
417.3
372.2
414.3
462.4
492.4
507.4
86
88
91
82
85
78
82
84
79
85
80
86
82
76
75
277–279
[300
C
C
C
C
15H11BrN4O2
15H10BrFN4O
15H10BrN5O3
16H13BrN4O3
[300
[300
257–259
239–241
213–215
231–233
[300
C9H7BrN6S
5a
5b
5c
5d
6
4-Hydroxy
4-Methyl
C
C
C
C
C
C
C
C
C
16H11BrN6OS
17H13BrN6S
16H10BrN7O2S
16H10BrFN6S
15H10BrN5S
18H16BrN5S
22H16BrN5S
23H18BrN5OS
22H15BrN6O2S
4-Nitro
4-Fluoro
[300
–
138–140
181–183
163–165
207–209
264–266
7a
7b
7c
7d
Propyl
Benzyl
4-Methoxybenzyl
4-Nitrobenzyl
protons of hydrazide 2 have disappeared, while new peaks
corresponding to phenyl ring and thiol group present on
triazole ring have appeared at d 7.5–7.1 and 2.07 ppm,
Table 2 Anticonvulsant screening results of final compounds 3a–3e,
4, 5a–5d, 6, and 7a–7d
Sample
MESa
0.5
scPTZa
0.5
Toxicity resultsa
1
respectively. Upon alkylation with propyl bromide, the H
4.0
4.0
0.5
4.0
NMR spectrum of product 7a displayed three characteristic
peaks at d 3.88, 1.67, and 0.97 ppm corresponding to two
methylene and the terminal methyl groups of propyl chain.
Its 13C NMR spectrum showed peaks at d 53.0, 20.77, and
10.86 ppm attributing to those alkyl protons, respectively,
confirming the conversion. In the same way, the structures
of all the final compounds were confirmed by their char-
acterization data and the same is summarized in the
experimental section. The physical data of target com-
pounds are given in Table 1.
3a
–
–
40
20
20
100
40
20
40
–
40
20
40
100
40
20
40
100
–
–
–
3b
–
40
–
–
–
3c
40
–
–
–
3d
–
–
–
3e
–
–
–
–
4
20
–
40
40
–
–
–
5a
–
–
5b
–
–
–
5c
–
–
–
–
–
5d
40
–
–
40
40
40
100
–
100
40
40
100
100
–
–
–
Anticonvulsant studies
6
100
40
–
–
–
7a
–
–
–
The in vivo animal models are the majorly used and widely
accepted methods for the investigation of preliminary
anticonvulsant activity in a newly synthesized compound.
The MES (Krall et al., 1978) and scPTZ (Clerk et al.,
1984) screening methods are the most important and
widely accepted techniques for the antiepileptic evaluation.
These two methods can detect new bioactive chemical
entities affording protection to seizures. Interestingly, all
the active AEDs are found to be active in at least one
among these two screening methods (Dawidowski et al.,
2012). Similarly, compounds found to be effective in either
of these screening methods are generally referred as
potential anticonvulsants (Wie˛ckowski et al., 2012).
Therefore in our present study, new derivatives were
screened for their antiepileptic properties following these
two methods. Further, the toxicity profile of new
7b
–
–
–
7c
–
–
–
–
7d
–
–
–
–
–
Phenytoin
Diazepam
20
x
20
x
x
x
100
–
100
–
20
20
The figures indicate the minimal concentration of sample required to
cause either protection or toxicity in more than 50 % of mice. The
dash (–) indicates the absence of activity/toxicity, while (x) denotes
not tested
a
Doses of 20, 40,and 100 mg/kg of the compounds were adminis-
tered, and the protection, as well as toxicity were measured after 0.5
and 4.0 h
compounds was evaluated by Rotarod method (Dunham
and Miya, 1957). These screening results are summarized
in Table 2.
123

Med Chem Res
The anticonvulsant results indicated that compounds 3b,
3c, 4, 5a, 5d, 6, 7a, and 7b were active in MES method,
while all the tested compounds except 5c and 7d were
active in scPTZ method. Among MES active compounds,
hydrazones carrying electron donating groups were found
to be more active than those containing electron with-
drawing substituents. Compound 4 carrying 4-amino-1,2,4-
triazole moiety displayed the highest activity at both the
intervals (0.5 and 4 h) indicating its fast onset and long
duration of action. On the other hand, most of the com-
pounds exhibited prominent activity in both the intervals as
indicated by the results of PTZ method. This clearly shows
that they can raise seizure threshold effectively (Stables
and Kupferberg, 1997). Compounds 3b and 4 exhibited
complete protection from seizure at 20 mg/kg dose and
their results are compared to that of standard drug
diazepam.
pronounced activity. The activity of 3b and 4 are compa-
rable with those of standard drug diazepam and so, they
can be considered as active templates for future develop-
mental studies.
Conclusions
Three new series of imidazo[1,2-a]pyridines carrying
hydrazone and triazole groups were successfully synthe-
sized. The structures of new derivatives were confirmed by
various spectral studies such as FTIR, 1H NMR, 13C NMR,
and mass spectral followed by elemental analysis studies.
The in vivo anticonvulsant studies of target compounds
were performed following MES and scPTZ methods, while
their toxicity study was carried out by Rotarod method.
The new compounds displayed better activity in scPTZ
method than that of MES method, which indicates their
ability to raise seizure threshold, effectively. Compounds
possessing electron donor groups showed pronounced
activity when compared with those of electron acceptor
analog. Particularly, compounds 3b and 4 carrying
hydroxyphenyl and 4-amino-1,2,4-triazole-3-thiol groups,
respectively, exhibited 100 % protection in scPTZ method,
and their results are comparable with those of standard
drug diazepam. Moreover, all the final compounds were
found to be nontoxic at all tested doses and so, they can be
considered as effective anticonvulsant agents.
The in vivo results indicated that the presence of elec-
tron donating groups on aryl groups enhances the anti-
convulsant property remarkably. This was evidenced by the
hydrazone derivatives (3a–3e), wherein compound 3a–3c
and 3e carrying electron donating groups were more active
than compound 3d that contains nitrophenyl moiety. The
compound 3b carrying 4-hydroxyphenyl group exhibited
complete protection from seizure at 20 mg/kg, which may
be attributed to the presence of hydrogen bond donating
hydroxyl group in the molecule. Similarly, 4-amino-1,2,4-
triazole derivative 4 carrying hydrogen bond donor, as well
as acceptor groups in the moiety showed similar activity
(100 % protection) in scPTZ method. Coupling of the
amine group with various aldehydes has led to decrease in
anticonvulsant activity. This clearly confirms the impor-
tance of amine group for enhanced anticonvulsant activity.
In Schiff bases 5a–d, more activity was observed for
compounds 5a, 5b, and 5d carrying electron donating
groups, viz. hydroxyphenyl, tolyl, and fluorophenyl groups,
respectively. In the same way, another 1,2,4-triazole-3-
thiol derivative 6 also displayed good activity at 40 mg/kg.
The same extent of activity was retained when the thiol
group was alkylated with propyl bromide. However,
replacement of propyl chain by benzyl rings resulted in
considerable decrease in their activity. The reason may be
due to the fact that the presence of more bulky groups
might disturb the direct ligand-receptor interaction by
inducing steric hindrance on the moiety.
Experimental
Chemistry
All the chemicals used in the present work were procured
from Sigma Aldrich and Lanchaster (UK). All the solvents
used were of analytical grade. They were purchased and
used as such without any further purification. The progress
of the reaction was monitored by thin layer chromatogra-
phy, performed on a Silica gel 60 F254 coated aluminum
sheet. Melting points were determined on open capillaries
using a Stuart SMP3 (BIBBY STERLIN Ltd. UK) appa-
ratus and were uncorrected. Infrared spectra were recorded
on a Nicolet Avatar 5700 FTIR (Thermo Electron Corpo-
1
ration). H NMR and 13C NMR spectra were recorded on
The toxicity study revealed that new imidazo[1,2-a]
pyridines are nontoxic at all tested doses. So, the new
compounds can be considered as nontoxic anticonvulsants.
In conclusion, the linking of imidazo[1,2-a]pyridines with
triazole and hydrazone moieties resulted in improved
activity without producing any toxicity upto 100 mg/kg.
Particularly, those hybrids possessing electron donating
and hydrogen bond donor/acceptor groups exhibited
Bruker-400 MHz FT-NMR spectrometer using TMS as
internal reference and DMSO-d6, CDCl3 as solvent. Ele-
mental analyses were performed on a Flash EA1112 CHNS
analyzer (Thermo Electron Corporation). Mass spectra
(ESI) were recorded on Waters ZQ-4000 liquid chroma-
tography-mass spectrometer. The synthesis of imidazo[1,2-a]
pyridine-2-carboxylate (1), its hydrazide (2) and various
123

Med Chem Res
hydrazones (3a–3e) were synthesized following reported
procedure (Turan-Zitoni et al., 2001).
refluxed for 6 h. The reaction vessel was cooled to room
temperature and the precipitated product was collected
by filtration. The product was washed well with ethanol
and purified by column chromatographic technique
using hexane: ethyl acetate (9:1) eluting system. Other
derivatives were also synthesized following similar
procedures.
Procedure for the synthesis of ethyl 6-bromo-
imidazo[1,2-a]pyridine-2-carboxylate (1)
A mixture of 5-bromo-2-aminopyridine (1 g, 5.78 mmol)
and ethyl bromopyruvate (1.13 g, 5.78 mmol) in 15 mL of
ethanol was refluxed for 6 h. The solvent was removed
under reduced pressure, and resulting crude product was
quenched into ice cold water with stirring. The solid
product was isolated by filtration and dried. The product
was later recrystallized from ethyl acetate to obtain pure
product.
Yield 84 %, m.p. 63–65 °C. FTIR (ATR, cm-1): 2,897,
2,846, 1,697, 1,538, 1,213. 1H NMR (DMSO-d6, 400 MHz,
d ppm): 8.94 (s, 1H, ArH), 8.37 (s, 1H, CH), 7.56–7.53 (d,
1H, ArH, J = 12 Hz), 7.38–7.35 (d, 1H, ArH, J = 12 Hz),
4.00–3.97 (q, 2H, CH2, J = 8, 4 Hz), 0.96–0.91 (t, 3H,
CH3, J = 10 Hz). 13NMR (100 MHz, DMSO-d6): 169.7
(C=O), 150.7 (PyC, C=N), 142.7 (ArC, C=N), 139.3 (PyC,
C=N), 124.1(ArC, C=N), 123.3 (PyC), 117.6 (PyC), 115.3
(PyC), 61.8 (OCH2), 13.8 (CH3). MS (m/z): 270.3. Anal.
Calcd. for C10H9BrN2O2: C, 44.63; H, 3.37; N, 10.41.
Found: C, 44.59; H, 3.38; N, 10.40.
6-Bromo-N’-(thiophen-2-ylmethylene)-imidazo[1,2-a]
pyridine-2-carbohydrazide (3a) FTIR (ATR, cm-1):
1
3,297, 3,077, 2,925, 1,670, 1,592, 1,549, 1,476, 1,199. H
NMR (DMSO-d6, 400 MHz, d ppm): 11.89 (s, 1H, NH),
8.96 (s, 1H, ArH), 8.55 (s, 1H, CH), 8.46 (s, 1H, CH),
7.631–7.608 (d, 1H, ArH, J = 9.2 Hz), 7.511–7.486
(d, 1H, ArH, J = 9.2 Hz), 7.39–7.18 (m, 3H, ArH).
13NMR (100 MHz, DMSO-d6): 164.3 (C=O), 158.2 (PyC,
C=N), 146.7 (ArC, C=N), 141.8 (PyC, C=N), 139.2 (ArH,
C=N), 131.2 (ArC), 129.2 (ArC), 127.1 (ArC), 118.9
(ArC), 117.6 (PyC), 115.8 (PyC), 107.3 (HC=N). MS
(m/z): 350.7. Anal. Calcd. for C13H9BrN4OS: C, 44.71; H,
2.60; N, 16.04. Found: C, 44.73; H, 2.61; N, 16.04.
N’-(4-Hydroxybenzylidene)-6-bromo-imidazo[1,2-a]
pyridine-2-carbohydrazide (3b) FTIR (ATR, cm-1):
1
3,323, 3,283, 3,092, 1,668, 1,599, 1,516, 1,434, 1,274. H
NMR (DMSO-d6, 400 MHz, d ppm): 11.90 (s, 1H, NH),
9.05 (s, 1H, OH), 8.96 (s, 1H, ArH), 8.57 (s, 1H, CH), 8.47
(s, 1H, CH), 7.712–7.692 (d, 2H, ArH, J = 8.0 Hz),
7.630–7.609 (d, 1H, ArH, J = 8.4 Hz), 7.514–7.493
(d, 1H, ArH, J = 8.4 Hz), 7.223–7.203 (d, 2H, ArH,
J = 8.0 Hz). 13C NMR (100 MHz, DMSO-d6): 164.3
(C=O), 161.6 (C–OH), 150.2 (PyC, C=N), 146.7 (ArC,
C=N), 142.3 (PyC, C=N), 139.0 (ArC, C=N), 130.7 (ArC),
129.3 (ArC), 127.4 (ArC), 118.6 (ArC), 116.1 (ArC), 115.7
(ArC), 107.3 (HC=N). MS (m/z): 360.3. Anal. Calcd. for
C15H11BrN4O2: C, 50.16; H, 3.09; N, 15.60. Found: C, 50.
14; H, 3.09; N, 15.61.
Procedure for the synthesis of 6-bromo-imidazo[1,2-a]
pyridine-2-carbohydrazide (2)
The ethyl carboxylate derivative 1 (0.8 g, 2.97 mmol) was
refluxed with hydrazine hydrate (0.3 g, 6.0 mmol) in eth-
anolic media for about 6 h. Upon completion of reaction,
the reaction mixture was cooled in deep freezer so as to get
solid product 2, that later filtered, dried, and recrystallized
from ethanol.
Yield 81 %, m.p. 183–186 °C. FTIR (ATR, cm-1):
3,448, 3,256, 3,159, 3,065, 1,677, 1,627, 1,561, 1,476,
1,279. 1H NMR (DMSO-d6, 400 MHz, d ppm): 9.89 (s, 1H,
NH), 8.60 (s, 1H, ArH), 8.23 (s, 1H, CH), 7.770–7.447 (d,
1H, ArH, J = 9.2 Hz), 7.194–7.171 (d, 1H, ArH,
J = 9.2 Hz), 4.28 (s, 2H, NH2). 13NMR (100 MHz,
DMSO-d6): 165.3 (C=O), 150.8 (PyC, C=N), 140.3 (ArC
C=N), 138.7 (PyC, C=N), 126.3 (ArC, C=N), 124.7 (PyC),
118.7 (PyC), 116.4 (PyC). MS (m/z): 257.3. Anal. Calcd.
for C8H7BrN4O: C, 37.67; H, 2.77; N, 21.97. Found: C,
37.65; H, 2.75; N, 21.98.
N’-(4-Fluorobenzylidene)-6-bromo-imidazo[1,2-a]
pyridine-2-carbohydrazide (3c) FTIR (ATR, cm-1):
1
3,300, 3,137, 3,070, 1,665, 1,600, 1,552, 1,488, 1,201. H
NMR (DMSO-d6, 400 MHz, d ppm): 11.94 (s, 1H, NH),
8.96 (s, 1H, ArH), 8.58 (s, 1H, CH), 8.46 (s, 1H, CH),
7.766–7.745 (d, 2H, ArH, J = 8.4 Hz), 7.631–7.607 (d, 1H,
ArH, J = 9.6 Hz), 7.511–7.487 (d, 1H, ArH, J = 9.6 Hz),
7.309–7.288 (d, 2H, ArH, J = 8.4 Hz). 13C NMR
(100 MHz, DMSO-d6): 164.2 (C=O), 161.8 (ArC, C–F),
158.1 (PyC, C=N), 147.0 (ArC, C=N), 142.4 (PyC, C=N),
139.1 (ArC, C=N), 131.0 (ArC), 129.5 (ArC), 127.4 (ArC),
118.3 (ArC), 115.9 (ArC), 107.1 (HC=N). MS (m/z): 361.
9. Anal. Calcd. for C15H10BrFN4O: C, 49.88; H, 2.79; N,
15.51. Found: C, 49.90; H, 2.78; N, 15.51.
General procedure for the synthesis of hydrazones (3a–e)
The hydrazide 2 (0.5 g, 1.96 mmol) was treated with
thiophene-2-aldehyde (0.22 g, 1.96 mmol) in 10 mL of
ethanol solution. A drop of concentrated sulfuric acid
was added as a dehydrating agent and the solution was
123

Med Chem Res
N’-(4-Nitrobenzylidene)-6-bromo-imidazo[1,2-a]pyridine-
2-carbohydrazide (3d) FTIR (ATR, cm-1): 3,297, 3,077,
(C=S), 142.7 (PyC, C=N), 131.4 (PyC, C=N), 129.3 (ArC,
C=N), 127.5 (ArC), 118.4 (ArC), 114.9 (ArC), 106.8 (C–
N). MS (m/z): 313.5. Anal. Calcd. for C9H7BrN6S: C,
34.74; H, 2.27; N, 27.01. Found: C, 34.71; H, 2.26; N,
27.02.
1
2,925, 1,670, 1,592, 1,549, 1,476, 1,334, 1,199. H NMR
(DMSO-d6, 400 MHz, d ppm): 11.95 (s, 1H, NH), 8.96 (s,
1H, ArH), 8.59 (s, 1H, CH), 8.46 (s, 1H, CH), 8.124–8.103
(d, 2H, ArH, J = 8.4 Hz), 7.632–7.609 (d, 1H, ArH, J =
9.2 Hz), 7.51–7.48 (m, 3H, ArH). 13C NMR (100 MHz,
DMSO-d6): 164.3 (C=O), 161.9 (ArC, C–NO2), 160.2
(PyC, C=N), 147.3 (ArC, C=N), 142.6 (PyC, C=N), 139.3
(ArC, C=N), 131.4 (ArC), 128.9 (ArC), 127.4 (ArC), 118.7
(ArC), 116.1 (ArC), 107.2 (HC=N). MS (m/z): 389.2. Anal.
Calcd. for C15H10BrN5O3: C, 46.41; H, 2.60; N, 18.04.
Found: C, 46.39; H, 2.60; N, 18.03.
General procedure for the synthesis of Schiff bases (5a–5d)
A mixture of triazole 4 (0.4 g, 1.29 mmol) with 4-hydroxy
benzaldehyde (0.19 g, 1.5 mmol) in 10 mL of ethanol was
refluxed for 6 h in presence of a drop of concentrated
sulfuric acid. The product 5a that precipitated out during
the course of reaction was filtered, washed with ethanol and
dried. The crude product was recrystallized from ethylene
dichloride to obtain pure compound. Similarly, other
derivatives were also synthesized.
N’-(4-Hydroxy-3-methoxybenzylidene)-6-bromo-imidazo
[1,2-a]pyridine-2-carbo hydrazide (3e) FTIR (ATR,
cm-1): 3,382, 3,327, 3,063, 2,934, 1,670, 1,583, 1,464,
1
1,231. H NMR (DMSO-d6, 400 MHz, d ppm): 11.93 (s,
4-((3-(6-Bromo-imidazo[1,2-a]pyridin-2-yl)-5-mercapto-
4H-1,2,4-triazol-4-ylimino) methyl)phenol (5a) FTIR
(ATR, cm-1): 3,412, 3,068, 2,884, 2,740, 1,620, 1,502,
1,417, 1,319, 1,148, 1,109. 1H NMR (DMSO-d6, 400 MHz,
d ppm): 14.12 (s, 1H, NH), 10.41 (s, 1H, OH), 9.51 (s, 1H,
CH), 9.07 (s, 1H, ArH), 8.40 (s, 1H, CH), 7.861–7.839 (d,
2H, ArH, J = 8.8 Hz), 7.755–7.734 (d, 1H, ArH, J =
8.4 Hz), 7.667–7.645 (d, 2H, ArH, J = 8.8 Hz), 7.454–7.
433 (d, 1H, ArH, J = 8.4 Hz). 13C NMR (100 MHz,
DMSO-d6): 177.1 (C=S), 163.2 (ArC, C–OH), 161.9 (PyC,
C=N), 144.2 (PyC, C=N), 132.0 (ArC, C=N), 130.1 (ArC),
129.1 (ArC), 127.5 (ArC), 122.7 (ArC), 118.4 (ArC), 115.7
(N=C–N), 107.5 (HC=N). MS (m/z): 416.3. Anal. Calcd.
for C16H11BrN6OS: C, 46.28; H, 2.67; N, 20.24. Found: C,
46.25; H, 2.66; N, 20.24.
1H, NH), 9.10 (s, 1H, OH), 8.96 (s, 1H, ArH), 8.58 (s, 1H,
CH), 8.45 (s, 1H, CH), 7.632–7.610 (d, 1H, ArH, J =
8.8 Hz), 7.511–7.489 (d, 1H, ArH, J = 8.8 Hz), 7.462–7.
443 (d, 1H, ArH, J = 7.6 Hz), 7.36 (s, 1H, ArH), 7.289–7.
270 (d, 1H, ArH, J = 7.6 Hz), 3.98 (s, 3H, CH3). 13C NMR
(100 MHz, DMSO-d6): 164.2 (C=O), 161.4 (ArC), 154.3
(PyC, C=N), 150.2 (ArC, C=N), 146.8 (PyC, C=N), 142.3
(ArC), 139.4 (ArC, C=N), 130.6 (ArC), 129.9 (ArC), 129.2
(ArC), 120.3 (ArC), 118.6 (ArC), 117.9 (ArC), 107.2 (HC=
N), 64.2 (OCH3). MS (m/z): 390.8. Anal. Calcd. for
C16H13BrN4O3: C, 49.38; H, 3.37; N, 14.40. Found: C,
49.35; H, 3.38; N, 14.40.
Procedure for the synthesis of 4-amino-5-(6-
bromoimidazo[1,2-a]pyridin-2-yl)-4H-1,2,
4-triazole-3-thiol (4)
4-(4-Methylbenzylideneamino]-5-(6-bromoH-imidazo[1,2-a]
pyridin-2-yl)-4H-1,2,4-triazole-3-thiol (5b) FTIR (ATR,
cm-1): 3,343, 2,978, 2,885, 2,765, 1,629, 1,521, 1,418,
1,319, 1,259, 1,148. 1H NMR (DMSO-d6, 400 MHz, d
ppm): 14.12 (s, 1H, NH), 9.51 (s, 1H, CH), 9.10 (s, 1H, ArH),
8.41 (s, 1H, CH), 7.75–7.70 (m, 3H, ArH), 7.457–7.437
(d, 1H, ArH, J = 8.0 Hz), 7.234–7.213 (d, 2H, ArH,
J = 8.4 Hz), 2.34 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6): 176.5 (C=S), 163.2 (PyC, C=N), 161.7 (PyC,
C=N), 145.0 (ArC), 143.4 (ArC), 131.4 (ArC), 129.4
(ArC), 127.5 (ArC), 122.3 (ArC), 121.1 (ArC), 118.4
(ArC), 116.1 (N=C–N), 107.5 (HC=N), 14.3 (CH3). MS
(m/z): 414.1. Anal. Calcd. for C17H13BrN6S: C, 49.40;
H, 3.17; N, 20.33. Found: C, 49.38; H, 3.16; N, 20.34.
An ethanolic solution of KOH was prepared by dissolving
0.2 g (3.6 mmol) of KOH in 10 mL of ethanol. To this
solution, hydrazide 2 (0.5 g, 1.96 mmol) and carbon
disulfide (0.3 g, 3.94 mmol) were added and the resulting
mixture was stirred at ambient temperature for about 8 h to
get potassium salt. Later, this mixture was stirred with
hydrazine hydrate (0.2 g, 4 mmol) at reflux condition for
6 h. Upon completion of reaction, the solvent was removed
and quenched into ice cold water. The mixture was neu-
tralized with hydrochloric acid to get solid product that
later isolated by filtration. The product was recrystallised
with ethanol-chloroform mixture.
FTIR (ATR, cm-1): 3,174, 3,098, 2,916, 2,771, 1,636,
1
1,591, 1,410, 1,319, 1,223, 1,167. H NMR (DMSO-d6,
4-(4-Nitrobenzylideneamino)-5-(6-bromo-imidazo[1,2-a]
pyridin-2-yl)-4H-1,2,4-triazole-3-thiol (5c) FTIR (ATR,
cm-1): 3,189, 3,031, 2,954, 2,834, 2,772, 1,618, 1,545,
1,247, 1,164. 1H NMR (DMSO-d6, 400 MHz, d ppm):
14.15 (s, 1H, NH), 9.52 (s, 1H, CH), 9.17 (s, 1H, ArH),
400 MHz, d ppm): 13.88 (s, 1H, H–NC=S), 9.06 (s, 1H,
ArH), 8.55 (s, 1H, CH), 7.768–7.747 (d, 1H, ArH,
J = 8.4 Hz), 7.164–7.143 (d, 1H, ArH, J = 8.4 Hz), 5.91
(s, 2H, NH2). 13C NMR (100 MHz, DMSO-d6): 166.1
123

Med Chem Res
8.41 (s, 1H, CH), 8.176–8.154 (d, 2H, ArH, J = 8.8 Hz),
7.59–7.43 (d, 4H, ArH). 13C NMR (100 MHz, DMSO-d6):
176.5 (C=S), 164.3 (PyC, C=N), 161.8 (PyC, C=N), 160.4
(ArC, C=NO2), 144.5 (ArC, C=N), 143.2 (ArC, C=N), 131.
8 (ArC), 131.0 (ArC), 128.9 (ArC), 127.8 (ArC), 122.8
(ArC), 116.7 (N=C–N), 107.6 (HC=N). MS (m/z): 445.7.
Anal. Calcd. for C16H10BrN7O2S: C, 43.26; H, 2.27; N,
22.07. Found: C, 43.25; H, 2.25; N, 22.06.
dry DMF (10 mL) was stirred at 60 °C for 6 h. The reac-
tion mixture was later quenched into ice water with stir-
ring. The precipitated product was filtered, washed with
water, and dried. The compound was purified by column
chromatography using hexane: ethyl acetate eluent system.
In the same way, other compounds were also synthesized.
6-Bromo-2-(4-phenyl-5-(propylthio)-4H-1,2,4-triazol-3-yl)
-imidazo[1,2-a]pyridine (7a) FTIR (ATR, cm-1): 3,091,
2,966, 2,873, 1,577, 1,494, 1,387, 1,229. 1H NMR (DMSO-
d6, 400 MHz, d ppm): 8.88 (s, 1H, ArH), 8.40 (s, 1H, CH),
7.60–7.18 (m, 7H, ArH), 3.884–3.839 (t, 2H, SCH2, J =
9.0 Hz), 1.67–1.59 (m, 2H, CH2), 0.975–0.937 (t, 3H, CH3,
J = 7.6 Hz). 13C NMR (100 MHz, DMSO-d6): 162.6
(PyC, C=N), 154.6 (PyC, C=N), 148.1 (C–S), 143.6 (ArC,
C=N), 141.2 (ArC, C=N), 130.7 (ArC), 129.8 (ArC), 126.0
(ArC), 124.8 (ArC), 122.6 (ArC), 118.1 (ArC), 113.7 (ArC),
107.1 (C=N), 53.0 (SCH2), 20.77 (CH2), 10.86 (CH3). MS
(m/z): 415.3. Anal. Calcd. for C18H16BrN5S: C, 52.18; H,
3.89; N, 16.90. Found: C, 52.16; H, 3.88; N, 16.90.
4-(4-Fluorobenzylideneamino)-5-(6-bromo-imidazo[1,2-a]
pyridin-2-yl)-4H-1,2,4-triazole-3-thiol (5d) FTIR (ATR,
cm-1): 3,203, 3,048, 2,950, 2,803, 2,734, 1,631, 1,587,
1,510, 1,417, 1,237. 1H NMR (DMSO-d6, 400 MHz, d ppm):
14.12 (s, 1H, NH), 9.51 (s, 1H, CH), 9.12 (s, 1H, ArH),
8.41 (s, 1H, CH), 7.864–7.843 (d, 2H, ArH, J = 8.4 Hz),
7.516–7.494 (d, 1H, ArH, J = 8.8 Hz), 7.453–7.431 (d, 1H,
ArH, J = 8.8 Hz), 7.332–7.311 (d, 2H, ArH, J = 8.4 Hz).
13C NMR (100 MHz, DMSO-d6): 174.1 (C=S), 165.4 (PyC),
163.1 (PyC), 159.6 (ArC, C–F), 144.5 (ArC, C=N), 142.7
(ArC, C=N), 134.6 (ArC), 129.7 (ArC), 123.4 (ArC), 121.3
(ArC), 119.4 (ArC), 115.4 (N=C–N), 107.6 HC=N). MS
(m/z): 418.4. Anal. Calcd. for C16H10BrFN6S: C, 46.06; H,
2.42; N, 20.14. Found: C, 46.04; H, 2.43; N, 20.14.
2-(5-(Benzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-6-bromo-
imidazo[1,2-a]pyridine (7b) FTIR (ATR, cm-1): 3,056,
1
2,916, 1,634, 1,578, 1,492, 1,213. H NMR (DMSO-d6,
Procedure for the synthesis of 5-(6-bromoimidazo[1,2-a]
400 MHz, d ppm): 8.88 (s, 1H, ArH), 8.39 (s, 1H, CH),
7.54–7.10 (m, 12H, ArH), 4.84 (s, 2H, SCH2). 13C NMR
(100 MHz, DMSO-d6): 162.3 (PyC, C=N), 160.2 (PyC, C=
N), 154.7 (C–S), 148.6 (ArC, C=N), 143.3 (ArC, C=N),
130.6 (ArC), 129.5 (ArC), 127.4 (ArC), 126.3 (ArC), 125.0
(ArC), 123.5 (ArC), 118.7 (ArC), 117.0 (ArC), 115.6
(ArC), 107.2 (C=N), 68.4 (SCH2). MS (m/z): 463.6. Anal.
Calcd. for C22H16BrN5S: C, 57.15; H, 3.49; N, 15.15.
Found: C, 57.12; H, 3.48; N, 15.14.
pyridin-2-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (6)
The hydrazide 2 (0.5 g, 1.96 mmol) was refluxed with
phenyl isothiocyanate (0.27 g, 1.96 mmol) in ethanol
(10 mL) medium for 8 h. The resulting thiosemicarbazide
derivatives was isolated through filtration, washed well
with ethanol and dried. This intermediate was later treated
with 2 N NaOH and stirred the resulting solution at 80 °C
for about 4 h. The reaction mixture was cooled to room
temperature and quenched to ice cold water while stirring.
The mixture was neutralized with conc. hydrochloric acid
and the precipitate thus obtained was filtered, washed with
excess of cold water. The pure product 6 was obtained by
recrystalising crude compound from ethanol.
FTIR (ATR, cm-1): 3,073, 2,361, 1,648, 1,595, 1,529,
1,501, 1,454, 1,357, 1,232. 1H NMR (DMSO-d6, 400 MHz,
d ppm): 8.96 (s, 1H, ArH), 8.42 (s, 1H, CH), 7.635–7.611 (d,
1H, ArH, J = 9.6 Hz), 7.53–7.10 (m, 6H, ArH), 2.07 (s, 1H,
SH). 13C NMR (100 MHz, DMSO-d6): 142.3 (PyC, C=N),
139.2 (PyC, C=N), 138.6 (C–S), 129.4 (ArC), 128.6 (ArC),
127.6 (ArC), 124.7 (ArC), 118.4 (ArC), 115.7 (ArC), 107.0
(C=N). MS (m/z): 372.9. Anal. Calcd. for C15H10BrN5S: C,
48.40; H, 2.71; N, 18.81. Found: C, 48.37; H, 2.70; N, 18.80.
2-(5-(4-Methoxybenzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-
6-bromo-imidazo[1,2-a]pyridine (7c) FTIR (ATR, cm-1):
1
3,000, 2,938, 2,834, 1,632, 1,579, 1,503, 1,238. H NMR
(DMSO-d6, 400 MHz, d ppm): 8.87 (s, 1H, ArH), 8.39 (s,
1H, CH), 7.641–7.620 (d, 2H, ArH, J = 8.4 Hz), 7.543–7.520
(d, 1H, ArH, J = 9.2 Hz), 7.51–7.08 (m, 8H, ArH), 4.82
(s, 2H, SCH2), 4.03 (s, 3H, OCH3). 13C NMR (100 MHz,
DMSO-d6): 162.3 (PyC, C=N), 159.6 (ArC, C–OMe),
153.9 (PyC, C=N), 147.6 (C–S), 140.4 (ArC, C=N), 138.7
(ArC, C=N), 130.3 (ArC), 128.7 (ArC), 127.5 (ArC), 124.3
(ArC), 122.6 (ArC), 121.0 (ArC), 119.8 (ArC), 107.6 (C=
N), 68.5 (SCH2), 63.7 (OCH3). MS (m/z): 493.5. Anal.
Calcd. for C23H18BrN5OS: C, 56.10; H, 3.68; N, 14.22.
Found: C, 56.11; H, 3.69; N, 14.22.
General procedure for the synthesis of 7a–7d
2-(5-(4-Nitrobenzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-6-
bromoH-imidazo[1,2-a]pyridine (7d) FTIR (ATR, cm-1):
3,066, 1,638, 1,585, 1,503, 1,334, 1,279. 1H NMR (DMSO-d6,
A mixture of 6 (0.4 g, 1.07 mmol), propyl bromide (0.2 g,
1.6 mmol) and potassium carbonate (0.3 g, 2.17 mmol) in
123

Med Chem Res
400 MHz, d ppm): 8.89 (s, 1H, ArH), 8.40 (s, 1H, CH),
8.145–8.124 (d, 2H, ArH, J = 8.4 Hz), 7.643–7.622
(d, 2H, ArH, J = 8.4 Hz), 7.545–7.521 (d, 1H, ArH, J =
9.6 Hz), 7.47–7.09 (m, 6H, ArH), 4.85 (s, 2H, SCH2). 13C
NMR (100 MHz, DMSO-d6): 163.2 (PyC, C=N), 161.4
(ArC, C–NO2), 158.7 (PyC, C=N), 154.6 (ArC, C=N), 146.
8 (C–S), 140.1 (ArC, C=N), 131.9 (ArC), 129.8 (ArC), 127.
5 (ArC), 125.4 (ArC), 123.5 (ArC), 123.0 (ArC), 120.3
(ArC), 119.5 (ArC), 107.3 (C=N), 68.6 (SCH2). MS (m/z):
508.6. Anal. Calcd. for C22H15BrN6O2S: C, 52.08; H, 2.98;
N, 16.56. Found: C, 52.06; H, 2.99; N, 16.55.
each of the three trials. The dose at which animal fell off
the rod, was determined. These experimental data are
presented in Table 2.
Acknowledgments The authors are thankful to National Institute of
Technology Karnataka, India for financial support and laboratory
facility, Indian Institute of Science, Bangalore for NMR facilities, and
SAIF Punjab for mass spectral facilities.
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Anticonvulsant studies
Maximal electroshock seizure (MES) test
The samples were injected to mice by suspending them in
2 % solution of Tween-80. Phenytoin was used as standard
drug to compare the effectiveness of target samples.
Groups of 6–10 male NMRI mice (18–30 g each) were
used to screen the samples. Electrical stimuli of 0.2 s in
duration (50 mA at 60 Hz) were delivered via corneal
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