Synthesis and characterization of nitrogen heterocyclic derivatives containing sulfur-ether and schiff base

Article abstract of DOI:10.1080/10426507.2012.761989

A series of new nitrogen heterocyclic compounds containing sulfur-ether (8a-8f) and Schiff-base (9a-9q) functionalities were synthesized by the reaction of the pharmaceutical lead compound containing both benzimidazole and 1,2,4-triazole rings. The compounds were characterized by ¹H NMR, ¹³C NMR, FT-IR, HR-MS, and ESI-MS.

Full text of DOI:10.1080/10426507.2012.761989

This article was downloaded by: [University of Saskatchewan Library]
On: 08 January 2015, At: 11:14
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis and Characterization of
Nitrogen Heterocyclic Derivatives
Containing Sulfur–Ether and Schiff Base
Jinyun Zheng a , Yujian Yu a , Xiaomin Zhen a , Erbing Yang a & Yufen
Zhao a b c
a Key Laboratory of Chemical Biology and Organic Chemistry of
Henan Province, College of Chemistry and Molecular Engineering ,
Zhengzhou University , Zhengzhou , China
b Department of Chemistry and Key Laboratory for Chemical Biology
of Fujian Province , Xiamen University , Xiamen , China
c Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical
Biology, Ministry of Education, Department of Chemistry , Tsinghua
University, Beijing , China
Accepted author version posted online: 25 Feb 2013.Published
online: 20 Sep 2013.
To cite this article: Jinyun Zheng , Yujian Yu , Xiaomin Zhen , Erbing Yang & Yufen Zhao (2013)
Synthesis and Characterization of Nitrogen Heterocyclic Derivatives Containing Sulfur–Ether and
Schiff Base, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:11, 1564-1575, DOI:
10.1080/10426507.2012.761989
To link to this article: http://dx.doi.org/10.1080/10426507.2012.761989
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.

This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 188:1564–1575, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.761989
SYNTHESIS AND CHARACTERIZATION OF NITROGEN
HETEROCYCLIC DERIVATIVES CONTAINING
SULFUR–ETHER AND SCHIFF BASE
Jinyun Zheng,1 Yujian Yu,1 Xiaomin Zhen,1 Erbing Yang,1 and
Yufen Zhao1,2,3
1Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province,
College of Chemistry and Molecular Engineering, Zhengzhou University,
Zhengzhou, China
2Department of Chemistry and Key Laboratory for Chemical Biology of Fujian
Province, Xiamen University, Xiamen, China
3Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology,
Ministry of Education, Department of Chemistry, Tsinghua University,
Beijing, China
GRAPHICAL ABSTRACT
Abstract A series of new nitrogen heterocyclic compounds containing sulfur–ether (8a–8f)
and Schiff-base (9a–9q) functionalities were synthesized by the reaction of the pharmaceutical
lead compound containing both benzimidazole and 1,2,4-triazole rings. The compounds were
characterized by 1H NMR, 13C NMR, FT-IR, HR-MS, and ESI-MS.
[Supplementary materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental
files: Additional figures.]
Received 12 November 2012; accepted 20 December 2012.
The authors would like to thank the National Natural Science Foundation Committee of China for financial
support to this work (No. 20732004).
Address correspondence to Jinyun Zheng, Key Laboratory of Chemical Biology and Organic Chemistry of
Henan Province, College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052,
China. E-mail: zhengjy@zzu.edu.cn
1564

NITROGEN HETEROCYCLIC DERIVATIVES
1565
INTRODUCTION
The benzimidazolenucleus is aconstituent of manybioactiveheterocycliccompounds
that are of wide interest because of their diverse biological and clinical applications.1 Benz-
imidazole derivatives have varied biological activities including antimicrobial,2 anticancer,3
antiviral,4 anti-inflammatory,5 antimycobacterial,6 anthelminthic7 properties. Therefore, in-
corporating of the benzimidazole nucleus into organic molecules is an important synthetic
strategy in pharmaceutical chemistry.
1,2,4-Triazole and its derivatives show a wide range of biological effects such as
antibacterial,8 antifungal,9 anticancer,10 anti-inflammatory,11 analgesic,12 anticonvulsant,13
antiviral,14 anti-HIV,15 and antidepressant16 activities. Thus, 1,2,4-triazole is a versatile lead
molecule for developing potential bioactive agents.
To search new compounds with higher biological activity and lower toxicity and
integrate the advantages of benzimidazole and 1,2,4-triazole, we designed a series of
double heterocyclic compounds containing both benzimidazole and 1,2,4-triazole as po-
tential pharmaceutical lead molecules. Furthermore, the lead molecules have two active
groups, namely, –NH2 and –SH. Because Schiff bases and thiols also play an important
role in the medicinal chemistry, and they are reported to show a variety of pharmaceuti-
cal properties.17–20 Therefore, we designed the heterocyclic derivatives containing amino
and thioether (Compounds 8) or Schiff base and thiol (Compounds 9). The new dou-
ble heterocyclic compounds were synthesized by a convenient method with high yields
(Figure 1), and target compounds were prepared by the improved method with short reactive
times.
Figure 1 Synthesis of compounds.

1566
J. ZHENG ET AL.
RESULTS AND DISCUSSION
Synthesis and Characterization
The new derivatives of heterocycles containing benzimidazole, 1,2,4-triazole and
active groups –NH2 and –SH were prepared by the typical heterocyclic synthesis method.
The o-phenylenediamine reacted with hydroxyacetic acid in the presence of hydrochloric
acid to yield 2-hydroxymethylbenzimidazole, then oxidization, esterification, hydrazinol-
ysis, salification, and finally cyclization formed compound 7. Due to the presence of –NH2
and –SH active groups, the structure of compound 7 can be modified easily. Its derivatives
of thioethers and Schiff bases were designed and synthesized, and compounds 8a–8f and
9a–9q were obtained with high yields (upon 85%) in a shorter time (2–4 h). It is worth
mentioning, in the synthesis process of compounds 9, general transformations were cat-
alyzed by concentrated sulfuric acid or hydrochloric acid using acetonitrile or methanol
as a solvent.21,22 The result is that using acetonitrile as solvent led to low yields and long
reaction times (more than 10 h). Glacial acetic acid was used as efficient solvent and catalyst
to synthesize compounds (9a–9q) in a shorter time (2–4 h, reflux) with higher yields. The
compounds are all solids with high melting points, easily precipitated, and purified, and
then the pure target compounds were obtained and characterized.
The 1H NMR and 13C NMR spectra of compounds 8a–8f were recorded, and the 1H
NMR spectrum of 8a is depicted in Figure 2 as a typical example. Figure 2 shows three
singlets at 4.52, 6.62, and 13.48 ppm attributed to methylene (–SCH2), amino (–NH2),
and imino group (–NH), respectively. The signals at 7.28–7.80 ppm are assigned to
the aromatic protons. The 13C NMR spectrum of 8a displayed 11 singlets belonging to
the different 11 carbons of the compound 8a. The signals at 153.3 and 146.3 ppm are
Figure 2 The 1H NMR spectrum of compound 8a.

NITROGEN HETEROCYCLIC DERIVATIVES
1567
assigned to the triazole’s carbons, and the signal at 141.0 ppm is assigned to the im-
idazole’s. The six singlets at 139.3, 137.8, 129.5, 128.9, 127.9, 122.8, and 112.5 ppm
belonged to the aromatic carbons. The signal of the saturated carbon (–SCH2) also found at
34.9 ppm.
The FT-IR spectrum of 8a showed a broad absorptions in the region of 3418 and
3296 cm−1 corresponding to the stretching vibration of N–H. The characteristic absorptions
for the vibration of the benzene ring were found at 1638, 1495, and 1454 cm−1. The bending
vibration of methylene group is also observed at 1419 cm−1
.
The H NMR and 13C NMR spectra of 9a–9q were recorded, and the H NMR
spectrum of 9f was depicted in Figure 3 as a typical example. There are four singlets in
low field with the integral of 1 at 9.20, 10.41, 13.25, and 14.45 ppm in Figure 3 belong to
–OH, –N CH, –NH, and –SH, respectively. The two doublets at 7.57 and 7.66 ppm are
assigned to the aromatic protons of benzimidazole moiety, and the remaining two doublets
for benzene ring protons were observed at 6.94 and 7.81 ppm, respectively. Other aromatic
protons resonated as a multiplet at 7.21–7.34 ppm. The 13C NMR spectrum of 9f showed
two signals at 163.9 and 141.8 ppm are assigned to the carbons of triazole. The singlets
at 162.5 and 139.4 ppm are attributed to carbon of –N CH– and imidazole, respectively.
While the other aromatic carbons also observed at 158.9, 138.9, 131.9, 124.7, 122.9, 116.5,
and 112.6 ppm.
1
1
The FT-IR spectrum of 9f showed three broad absorption bands at 3350, 3138, and
2608 cm−1 attributed to characteristic stretching vibration of O–H, N–H, and S–H. The
absorptions for the vibration of the benzene ring were found at 1570, 1516, and 1482 cm−1
.
The broad absorption band at 1604 cm−1 assigned to the stretching vibration of C N bond
was observed too.
Figure 3 The 1H NMR spectrum of compound 9f.

1568
J. ZHENG ET AL.
Table 1 ESI-MSn data of compounds 8a–8f
Fragment
ions (relative
abundance%)
Precursor
ions
Compounds
8a
323.1 (9)
361.0 (8)
345 (100)
229.9 (22)
203.9 (30)
143.8 (33)
359.1 (100)
232.9 (51)
288.0 (30)
143.9 (38)
359.1 (76)
288.1 (56)
218.0 (9)
217.9 (90)
143.9 (23)
(MW = 322)
323.1 (23)
306.8 (65)
218.0 (90)
337.1 (83)
337.2 (34)
321.1 (79)
233.0 (33)
337.1 (100)
337.1 (33)
144.0 (3)
320.1 (23)
337.1 (76)
337.1 (36)
143.9 (4)
320.1 (36)
353.2 (11)
353.2 (4)
307.1 (100)
229.9 (100)
188.8 (100)
375.1 (13)
321.1 (42)
304.1 (51)
217.0 (100)
375.1 (10)
321.1 (29)
105.1 (100)
288.1 (100)
375.1 (9)
321.1 (66)
105.0 (47)
304.0 (13)
375.1 (100)
336.5 (23)
269.0 (34)
230.9 (100)
201.9 (94)
143.9 (6)
91.2 (17)
8b
218.1 (25)
217.9 (37)
229.9 (100)
105.1 (23)
143.9 (2)
203.9 (49)
(MW = 336)
105.1 (100)
8c
218.1 (17)
233.0 (20)
105.1 (14)
217.9 (88)
(MW = 336)
229.9 (9)
359.1 (100)
233.0 (16)
8d
218.2 (21)
229.9 (12)
105.0 (12)
217.9 (100)
(MW = 336)
288.0 (11)
218.1 (7)
218.0 (16)
232.0 (44)
201.9 (33)
160.9 (90)
229.9 (100)
121.1 (9)
144.0 (4)
218.1 (6)
160.9 (7)
143.9 (100)
203.9 (24)
144.0 (10)
8e
(MW = 352)
121.1 (100)
144.0 (3)
144.0 (19)
8f
247.0 (100)
247.0 (23)
230.0 (24)
(MW = 246)
Positive Ion ESI-MS/MS Spectra of Compounds
The fragmentation experiments were performed using a Bruker Esquire 3000
electrospray ion trap mass spectrometer. Ionization of analytes was carried out using the
following setting of ESI: nebulizer gas flow 7 psi, dry gas 4 L/min, dry temperature 300 ◦C,
capillary voltage 4000 V. ESI-MSn spectra were obtained by collision induced dissociation
(CID) experiments with helium after isolation of the appropriate precursor ions, and the
isolation width was 2.0 m/z.
Compared with the ESI-MSn spectra of their positive molecular ions, the [M+H]+
ions of compounds 8 present relatively simple and orderly spectra. The ESI-MSn data of
compounds 8a–8f are shown in Table 1. The results showed that the [M+H]+ ions mainly
produced [M+H-16]+, [M+H-16-R1]+, [M+H-CHR1]+, [M+H-16-CHR1]+, [144]+, and
[105]+ six kinds of positive ions. By integrating the results of ESI-MSn data, the fragmen-
tation pathways were proposed as shown in Figure 4. It is worth noting that the [M+H]+
ions of compounds 8a–8f all produced ions at m/z 144, which might to form a tri-ring cyclic
compound.
The fragmentation patterns of [M+H]+ ion of compounds 9a–9q are little different
to those of compounds 8 due to the Schiff-base structure. The main fragment ions derived
from [M+H]+ ions were [M+H−R2CN]+, and m/z at 144 and 105 were also produced.
Solubility of Compounds
Because of their rigid and ring structures, compounds 8 and compounds 9 have
excellent solubility in polar aprotic solvents such as DMF and DMSO, but only slight

NITROGEN HETEROCYCLIC DERIVATIVES
1569
Figure 4 The proposed fragmentation pathways of compounds 8a–8f.
solubility in protonic solvents such as water and ethanol and low-polarity solvents such as
methylene chloride and chloroform. Phosphorylation of –NH2 or oxidation of –SH may be
improved their solubility in water and other solvents, which will be the focus of our next
work.
CONCLUSIONS
Two series of nitrogen heterocyclic compounds containing thioether or Schiff bases
were synthesized by the improved reaction method with high yields. The structures of all
compounds were determined by 1H NMR, 13C NMR, and FT-IR spectroscopies. The positive
ion ESI-MS/MS spectra of compounds were recorded, and the fragmentation patterns of
[M+H]+ were discussed. The biological activities and potential clinical applications of
compounds are under study.
EXPERIMENTAL
Instruments and Reagents
Melting point was recorded on a XT4A micro melting point determination instru-
ment. 1H-NMR and 13CPD-NMR spectra were on a Bruker AV 400 with deuterated DMSO
as solvents. Chemical shifts (δ values) are given in parts per million with tetramethylsi-
lane as an internal standard. ESI-MS and HR-MS were recorded on Bruker Esquire-3000
electrospray ion trap mass spectrometer and Water Q-Tof micro mass spectrometer, respec-
tively. Infrared spectra were recorded with a Bruker-Alpha spectrophotometer in the range
of 4000–400 cm−1; samples were prepared as KBr pellets.

1570
J. ZHENG ET AL.
Hydroxyacetic acid, 1,2-diaminobenzene, benzyl chlorides, substituent benzaldehy-
des, carbon disulfide, thionyl chloride, hydrazinium hydrate (80%), and other reagents were
used as supplied (AR).
The compound 2 was prepared from 1,2-diaminobenzene and hydroxyacetic acid
according to the literature,23 mp 170–171 ◦C. Using potassium permanganate oxidation of
◦
compound 2, compound 3 was obtained as white solid, mp 169–171 C.23 Compound 3
◦
reacted with thionyl chloride to obtain compound 4, mp 219–220 C. Compound 5 was
prepared by the compound 4 and hydrazine hydrate in ethanol,24 mp 242–243 ◦C.
Synthesis of Potassium Salt (Compound 6)
KOH (5.73 g, 102.17 mmol) was dissolved in anhydrous ethanol (200 mL), and
benzimidazole-2-carboxylic acid hydrazide (12.00 g, 68.12 mmol) was added. The solution
was cooled in an ice bath. Then carbon disulfide (6.12 mL, 102.17 mmol) was added in
small portions, and the reaction mixture was stirred for 40 h at room temperature. The
precipitated potassium dithiocarbamate was collected by filtration and was further washed
with anhydrous ether (3 × 20 mL) and dried under vacuum. The potassium salt was obtained
almost in quantitative yield and was used in the next step without further purification.
Synthesis of 4-Amino-5-(1H-benzimidazole-2-yl)-4H-[1,2,4]triazole-3-
thiol (Compound 7)
A suspension of potassium salt (6) (12.00 g, 41.32 mmol), ethanol (100 mL) and
hydrazine hydrate (80%, 11 mL) were placed in the flask and refluxed for 8 h. The reaction
mixture was cooled to room temperature and diluted with water (50 mL). The solution
was acidificated with concentrated hydrochloric acid, and the required triazole (6) was
precipitated out. Which was filtered, washed with cold water (3 × 30 mL), and recrystallized
from 90% ethanol to yield white solid of 8.85 g (yield 92.3%). Melting point: 249–250 ◦C.
Compound 7: 1H NMR (DMSO-d6) δ: 14.26 (s, 1H, –SH), 13.33 (s, 1H, –NH), 7.78
(d, J = 7.6 Hz, 1H, Ph–H), 7.63 (d, J = 8.0 Hz, 1H, Ph–H), 7.32 (m, 2H, Ph–H), 6.44
(s, 2H, –NH2); ESI-MS m/z: calcd for 233.06 [M+H]+, 255.04 [M+Na]+, found 233.0
[M+H]+, 255.0 [M+Na]+.
Synthesis of 3-(Benzylthio)-5-(1H-benzimidazol-2-yl)-4H-[1,2,4]triazole-
4-amine (Compound 8a)
Compounds 8a–8f were prepared by a similar synthetic procedure; compound 8a
is reported as the typical example: Compound 7 (0.40 g, 1.72 mmol) was suspended in
appropriate amount water, and KOH (0.069 g) was added under stirring at room temperature.
After 30–40 min, the solution was brought to 0 ◦C in an ice bath, and benzyl chloride
(0.44 g, 3.44 mmol) was dropped in with vigorous stirring. The reaction mixture was stirred
continuously for 3 h at room temperature with the appearance of a white precipitate. The
solid was filtered, washed with water, and recrystallized from methanol/DMF.
Characterization Data of Compounds 8a–8f
3-(Benzylthio)-5-(1H-benzimidazol-2-yl)-4H-[1,2,4]triazole-4-amine (Compou-
nd 8a): White solid; yield: 90.1%; mp: 246–247 ◦C; 1H NMR (DMSO-d6) δ/ppm: 13.48
(s, 1H, –NH), 7.77 (d, J = 8.0 Hz, 1H, Ph–H), 7.57 (d, J = 8.0 Hz, 1H, Ph–H), 7.48 (d, J =
7.2 Hz, 2H, Ph–H), 7.31 (m, 5H, Ph–H), 6.62 (s, 2H, –NH2), 4.52 (s, 2H, –CH2–); 13C NMR

NITROGEN HETEROCYCLIC DERIVATIVES
1571
(DMSO-d6) δ/ppm: 153.3, 146.3, 141.0, 139.3, 137.8, 129.5, 128.9, 127.9, 122.8, 112.5,
34.9; FT-IR (KBr) ν/cm−1: 3418 (N–H), 3296, 2895, 1638, 1495, 1454, 745, 711, 695;
ESI-MS m/z: 323.1 [M+H]+, 345.1 [M+Na]+; HR-MS: calcd for C16H15N6S [M+H]+
323.1079, found 323.1076.
3-(4-Methylbenzylthio)-5-(1H-benzimidazol-2-yl)-4H-◦[1,2,4]triazole-4-amine
1
(Compound 8b): White solid; yield: 88.6%; mp: 237–239 C; H NMR (DMSO-d6)
δ/ppm: 13.46 (s, 1H, –NH), 7.76 (d, J = 7.6 Hz, 1H, Ph–H), 7.57 (d, J = 7.6 Hz, 1H,
Ph–H), 7.31 (m, 4H, Ph–H), 7.13 (d, J = 7.2 Hz, 2H, Ph–H), 6.61 (s, 2H, –NH2), 4.47 (s,
2H, –CH2-), 2.28 (s, 3H, –CH3); 13C NMR (DMSO-d6) δ/ppm: 153.4, 146.4, 141.0, 139.3,
138.1, 132.0, 129.4, 128.6, 122.9, 112.6, 34.8, 21.2; FT-IR (KBr) ν/cm−1: 3416, 3310,
3206, 2979, 1642, 1513, 1416, 784, 746; ESI-MS m/z: 337.1 [M+H]+, 359.1 [M+Na]+;
HR-MS: calcd for C17H17N6S [M+H]+ 337.1235, found 337.1232.
3-(2-Methylbenzylthio)-5-(1H-benzimidazol-2-yl)-4H-◦[1,2,4]triazole-4-amine
1
(Compound 8c): White solid, yield: 92.0%; mp: 255–257 C; H NMR (DMSO-d6)
δ/ppm: 13.51 (s, 1H, –NH), 7.68 (s, 2H, Ph–H), 7.42 (d, J = 7.2 Hz, 1H, Ph–H), 7.23
(m, 5H, Ph–H), 6.65 (s, 2H, –NH2), 4.47 (s, 2H, –CH2-), 2.42 (s, 3H, –CH3); 13C NMR
(DMSO-d6) δ/ppm: 153.2, 146.3, 141.0, 139.4, 137.2, 135.2, 130.8, 130.4, 129.9, 128.3,
126.5, 122.9, 112.5, 33.5, 19.2; FT-IR (KBr) ν/cm−1: 3420, 3304, 3209, 2980, 1643, 1495,
1416, 742; ESI-MS m/z: 337.1 [M+H]+, 359.1 [M+Na]+.
3-(3-Methbenzylthio)-5-(1H-benzimidazol-2-yl)-4H-[1◦,2,4]triazole-4-amine
1
(Compound 8d): White solid; yield: 92.0%; mp: 230–231 C; H NMR (DMSO-d6)
δ/ppm: 13.49 (s, 1H, –NH), 7.77 (d, J = 7.2 Hz, 1H, Ph–H), 7.58 (d, J = 7.2 Hz, 1H,
Ph–H), 7.28 (m, 5H, Ph–H), 7.09 (d, J = 7.2 Hz, 2H, Ph–H), 6.63 (s, 2H, –NH2), 4.48 (s,
2H, –CH2-), 2.29 (s, 3H, –CH3); 13C NMR (DMSO-d6) δ/ppm: 153.6, 146.4, 140.9, 139.3,
138.1, 134.2, 128.8, 128.5, 126.6, 124.4, 122.9, 112.5, 34.9, 21.4; FT-IR (KBr) ν/cm−1
:
3421, 3303, 3272, 2970, 2893, 1639, 1623, 1485, 1420, 798, 743, 692; ESI-MS m/z: 337.1
[M+H]+, 359.1 [M+Na]+.
3-(4-Methoxybenzylthio)-5-(1H-benzimidazol-2-yl)-4H-[1,2,4]triazole-4-amine
◦
1
(Compound 8e): White solid; yield: 93.2%; mp: 247–249 C; H NMR (DMSO-d6)
δ/ppm: 13.46 (s, 1H, –NH), 7.76 (s, 1H, Ph–H), 7.56 (s, 1H, Ph–H), 7.39((d, J = 8.0 Hz,
2H, Ph–H), 7.30 (s, 2H, Ph–H), 6.89 (d, J = 7.6 Hz, 2H, Ph–H), 6.61 (s, 2H, –NH2), 4.46
(s, 2H, –CH2-), 3.73 (s, 3H, –OCH3); 13C NMR (DMSO-d6) δ/ppm:163.5, 153.4, 146.3,
141.0, 139.4, 129.4, 127.2, 122.8, 114.8, 55.8, 33.2; FT-IR (KBr) ν/cm−1: 3419, 3309,
3201, 2903, 2832, 1642, 1611, 1512, 1460, 835, 747.0; ESI-MS m/z: 353.2 [M+H]+,
375.1 [M+Na]+; HR-MS: calcd for C17H17N6OS [M+H]+ 353.1185, found 353.1187.
3-(3-Methylthio)-5-(1H-benzimidazol-2-yl)-4H-[1,2,4]triazole-4-amine (Comp-
ound 8f): White solid; yield: 95.8%; mp: 253–255 ◦C; 1H NMR (DMSO-d6) δ/ppm: 13.47
(s, 1H, –NH), 7.76 (d, J = 7.6 Hz, 1H, Ph–H), 7.56 (d, J = 8.0 Hz, 1H, Ph–H), 7.29 (m,
5H, Ph–H), 6.58 (s, 2H, –NH2), 2.67 (s, 3H, –CH3); 13C NMR (DMSO-d6) δ/ppm: 153.2,
146.4, 141.0, 139.8, 122.8, 112.5, 14.5; FT-IR (KBr) ν/cm−1: 3418, 3301, 3273, 2978,
1640, 1624, 1497, 1459, 742; ESI-MS m/z: 247.0 [M+H]+, 269.0 [M+Na]+; HR-MS:
calcd for C10H11N6S [M+H]+ 247.0766, found 247.0768.
Synthesis of 5-(1H-Benzimidazol-2-yl)-4-((2-methoxybenzylidene)
amino)-4H- [1,2,4]triazole-3-thiol (Compound 9a)
Compounds 9a–9q were prepared by the similar synthesis procedure. Here, com-
pound 9a is reported as the typical example: A solution of compound 7 (0.40 g, 1.72 mmol)

1572
J. ZHENG ET AL.
and 2-methoxybenzaldehyde (0.35 g, 2.58 mmol) in acetic acid (15 mL) was refluxed for 2 h
under electromagnetic stirring. The reaction mixture was cooled to room temperature, and
the solid was slowly precipitated out. It was filtered, washed with methanol (3 × 10 mL),
and recrystallized from methanol to obtain the pure compound 9a 0.565 g (yield: 93.6%).
Characterization Data of Products 9a–9q
Compound 9a: 1H NMR (DMSO-d6) δ/ppm: 14.51 (s, 1H, –SH), 13.24 (s, 1H, –NH),
9.77 (s, 1H, –N CH–), 8.06 (d, J = 7.6 Hz, 1H, Ph–H), 7.63 (m, 3H, Ph–H), 7.28 (m,
3H, Ph–H), 7.13 (t, J = 7.6 Hz, 1H, Ph–H), 3.90 (s, 3H, –OCH3); 13C NMR (DMSO-d6)
δ/ppm: 164.1, 163.7, 159.8, 142.1, 139.0, 138.9, 135.2, 127.9, 123.7, 121.3, 120.5, 112.6,
112.5, 56.4; FT-IR (KBr) ν/cm−1: 3443, 3273, 2739, 2418, 1691, 1597, 1521, 1479, 744;
ESI-MS m/z: 351.2 [M+H]+, 373.2 [M+Na]+; HR-MS: calcd for C17H15N6OS [M+H]+
351.1028, found 351.1025.
5-(1H-Benzimidazol-2-yl)-4-((3-methoxybenzylidene)amino)-4H-[1,2,4]triazo-
le-3-thiol (Compound 9b): White solid; yield: 88.3%; mp: 229–231 ◦C; 1H NMR
(DMSO-d6) δ/ppm: 14.54 (s, 1H, –SH), 13.31 (s, 1H, –NH), 9.4 (s, 1H, –N CH–), 7.67
(d, J = 8.0 Hz, 1H, Ph–H), 7.58 (d, J = 8.0 Hz, 1H, Ph–H), 7.51 (m, J = 7.4 Hz, 3H,
Ph–H), 7.33 (t, J = 7.6 Hz, 1H, Ph–H), 7.24 (m, 2H, Ph–H), 3.84 (s, 3H, –OCH3); 13C
NMR (DMSO-d6) δ/ppm: 165.9, 163.8, 160.1, 143.2, 141.9, 138.8, 137.4, 136.8, 133.8,
130.8, 122.5, 119.6, 113.5, 55.8; FT-IR (KBr) ν/cm−1: 3418, 3252, 2417, 1648, 1614,
1572, 1539,1487, 780, 735, 684; ESI-MS m/z: 351.2 [M+H]+, 373.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((4-methoxybenzylidene)amino)-4H-[1,2,4]triaz-
ole-3-thiol (Compound 9c): White solid; yield: 98.0%; mp: 247–248 ◦C; 1H NMR
(DMSO-d6) δ/ppm: 14.48 (s, 1H, –SH), 13.27 (s, 1H, –NH), 9.31 (s, 1H, –N CH–),
7.93 (d, J = 8.4 Hz, 2H, Ph–H), 7.66 (d, J = 8.0 Hz, 1H, Ph–H), 7.58 (d, J = 8.0 Hz,
1H, Ph–H), 7.32 (t, J = 7.4 Hz, 1H, Ph–H), 7.23 (t, J = 7.4 Hz, 1H, Ph–H), 7.14 (d,
J 8.4 Hz, 2H, Ph–H), 3.87 (s, 3H, –OCH3); 13C NMR (DMSO-d6) δ/ppm: 169.2, 163.9,
163.5, 141.8, 139.4, 138.9, 131.6, 124.9, 122.9, 115.1, 112.6, 56.0; FT-IR (KBr) ν/cm−1
:
3362, 2365, 1646, 1600, 1515, 1485, 1462, 832, 743; ESI-MS m/z: 351.1 [M+H]+, 373.1
[M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((2-hydroxy-3-methoxybenzylidene)amino)-4H-
[1,2,4] triazole-3-thiol (Compound 9d): Light yellow solid; yield: 88.3%; mp:
229–231 ◦C; 1H NMR (DMSO-d6) δ/ppm: 14.46 (s, 1H, –SH), 13.26 (s, 1H, –NH), 10.07
(s, 1H, –N CH ), 9.24 (s, 1H, OH), 7.67 (d, J = 8.0 Hz, 1H, Ph–H), 7.57 (d, J =
11.6 Hz, 2H, Ph–H), 7.38 (d, J = 7.6 Hz, 1H, Ph–H), 7.32 (t, J = 7.4 Hz, 1H, Ph–H), 7.24
(t, J = 7.4 Hz, 1H, Ph–H), 6.95 (d, J = 8.0 Hz, 1H, Ph–H), 3.84 (s, 3H, –OCH3); 13C
NMR (DMSO-d6) δ/ppm: 165.4, 163.9, 152.1, 148.6, 141.9, 139.4, 138.9, 125.4, 123.7,
122.5, 116.1, 115.9, 112.6, 56.1; FT-IR (KBr) ν/cm−1: 3422, 3354, 2396, 1649, 1588,
1512, 1483, 729; ESI-MS m/z: 367.1 [M+H]+, 377.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((3-hydroxybenzylidene)amino)-4H-[1,2,4]triazole-
3-thiol (Compound 9e): White solid; yield: 85.9%; mp: 231–233 ◦C; 1H NMR (DMSO-d6)
δ/ppm: 14.53 (s, 1H, –SH), 13.32 (s, 1H, –NH), 9.88 (s, 1H, –N CH–), 9.36 (s, 1H,
OH), 7.68 (d, J = 8.0 Hz, 1H, Ph–H), 7.58 (d, J = 8.0 Hz, 1H, Ph–H), 7.37 (m, 4H,
Ph–H), 7.24 (t, J = 7.2 Hz, 1H, Ph–H), 7.05 (m, 1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm:
165.9, 163.9, 158.3, 143.2, 141.9, 141.3, 138.9, 137.0, 133.6, 130.7, 121.5, 120.8, 114.8;
FT-IR (KBr) ν/cm−1: 3417, 3032, 2414, 1633, 1574, 1515, 1472, 786, 750; ESI-MS m/z:
337.1 [M+H]+, 359.1 [M+Na]+.

NITROGEN HETEROCYCLIC DERIVATIVES
1573
5-(1H-Benzimidazol-2-yl)-4-((4-hydroxybenzylidene)amino)-4H-[1◦,2,4]triazole-
1
3-thiol (Compound 9f): Light yellow solid; yield: 89.3%; mp: 236–237 C; H NMR
(DMSO-d6) δ/ppm: 14.45 (s, 1H, –SH), 13.25 (s, 1H, –NH), 10.41 (s, 1H, –N = CH–)
9.20 (s, 1H, -ArOH), 7.81 (d, J = 8.4 Hz, 2H, Ph–H), 7.67 (d, J = 8.0 Hz, 2H, Ph–H),
7.57 (d, J = 8.0 Hz, 1H, Ph–H), 7.32 (d, J = 7.6Hz, 1H, Ph–H), 7.23 (t, J = 7.6 Hz, 1H,
Ph–H), 6.94 (t, J = 8.0 Hz, 1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 163.9, 162.5, 158.9,
141.8, 139.4, 138.9, 131.9, 124.7, 122.9, 116.5, 112.6; FT-IR (KBr) ν/cm−1: 3428, 3350,
2608, 1604, 1570, 1516, 1482, 828, 745; ESI-MS m/z: 337.1 [M+H]+, 359.1 [M+Na]+;
HR-MS: calcd for C16H13N6OS [M+H]+ 337.0870, found 337.0879.
5-(1H-Benzimidazol-2-yl)-4-((4-methylbenzylidene)amino)-4H-[1,2,4]triazole-
◦
1
3-thiol (Compound 9g): Light yellow solid; yield: 91.3%; mp: 212–214 C; H NMR
(DMSO-d6) δ/ppm: 14.51(s, 1H, –SH), 13.29 (s, 1H, –NH), 9.39 (s, 1H, –N = CH–),
7.87 (d, J = 7.6 Hz, 2H, Ph–H), 7.66 (d, J = 8.0 Hz, 1H, Ph–H), 7.58 (d, J = 8.0 Hz,
1H, Ph–H), 7.40 (d, J = 7.6 Hz, 2H, Ph–H), 7.32 (t, J = 7.4 Hz, 1H, Ph–H), 7.23 (t,
J = 7.4 Hz, 1H, Ph–H), 2.42 (s, 3H, CH3); 13C NMR (DMSO-d6) δ/ppm: 165.9, 163.9,
143.8, 141.8, 139.3, 138.9, 130.2, 129.8, 129.6, 122.5, 112.4, 21.8; FT-IR (KBr) ν/cm−1
:
3362, 2367, 1648, 1600, 1566, 1534, 1479, 814, 752; ESI-MS m/z: 335.2 [M+H]+, 357.2
[M+Na]+; HR-MS: calcd for C17H15N6S [M+H]+ 335.1079, found 335.1077.
5-(1H-Benzimidazol-2-yl)-4-((4-bromobenzylidene)amino)-4H-[1,2,4]triazole-
3-thiol (Compound 9h): Yellow solid; yield: 90.5%; mp: 193–195 ◦C; 1H NMR
(DMSO-d6) δ/ppm: 14.56 (s, 1H, –SH), 13.32 (s, 1H, –NH), 9.52 (s, 1H, –N CH–), 7.93
(d, J = 8.0 Hz, 2H, Ph–H), 7.81 (d, J = 8.4 Hz, 2H, Ph–H), 7.66 (d, J = 8.0 Hz, 1H,
Ph–H), 7.58 (d, J = 7.6 Hz, 1H, Ph–H), 7.33 (t, J = 7.4 Hz, 1H, Ph–H), 7.24 (t, J 7.4 Hz,
1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 165.9, 163.8, 141.8, 141.1, 138.8, 132.7, 131.3,
128.9, 125.6, 122.6, 112.4; FT-IR (KBr) ν/cm−1: 3340, 2402, 1644, 1589, 1524, 1478,
818, 747, 527; ESI-MS m/z: 399.0, 401.0 [M+H]+, 421.1, 423.0 [M+Na]+; HR-MS: calcd
for C16H12BrN6S [M+H]+ 399.0028, found 399.0027.
5-(1H-Benzimidazol-2-yl)-4-((3-bromobenzylidene)amino)-4H-[1,2,4]triazole-
3-thiol (Compound 9i): Yellow solid; yield: 88.3%; mp: 170–172 ◦C; 1H NMR
(DMSO-d6) δ/ppm: 14.58 (s, 1H, –SH), 13.31 (s, 1H, –NH), 9.49 (s, 1H, –N CH–), 8.19
(s, 1H, Ph–H), 7.98 (d, J = 7.6 Hz, 1H, Ph–H), 7.88 (m, 1H, Ph–H), 7.68 (d, J = 8.4 Hz,
1H, Ph–H), 7.56 (m, 2H, Ph–H), 7.34 (t, J = 7.6 Hz, 1H, Ph–H), 7.25 (t, J = 7.8 Hz, 1H,
Ph–H); 13C NMR (DMSO-d6) δ/ppm: 166.0, 163.8, 141.9, 141.1, 138.7, 135.8, 134.7,
131.6, 129.7, 128.7, 124.4, 122.7, 111.7; FT-IR (KBr) ν/cm−1: 3320, 2419, 1649, 1592,
1534, 1482, 793, 731, 528; ESI-MS m/z: 399.0,401.0 [M+H]+, 421.1,423.0 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((2-bromobenzylidene)amino)-4H-[1,2◦,4]triazole-
1
3-thiol (Compound 9j): Light yellow solid; yield: 90.8%; mp: 179–181 C; H NMR
(DMSO-d6) δ/ppm: 14.60 (s, 1H, –SH), 13.28 (s, 1H, –NH), 10.13 (s, 1H, –N CH–), 8.24
(t, J = 4.2 Hz, 1H, Ph–H), 7.85 (t, J = 4.0 Hz, 1H, Ph–H), 7.72 (d, J = 8.0 Hz, 1H, Ph–H),
7.59 (d, J = 5.2 Hz, 3H, Ph–H), 7.34 (t, J = 7.6 Hz, 1H, Ph–H), 7.26 (t, J = 7.6 Hz, 1H,
Ph–H); 13C NMR (DMSO-d6) δ/ppm: 165.2, 163.5, 142.2, 139.4, 138.8, 134.9, 134.0,
131.7, 129.3, 128.9, 126.1, 123.0, 112.7; FT-IR (KBr) ν/cm−1: 3383, 3246, 2424, 1645,
1588, 1529, 1479, 748, 528; ESI-MS m/z: 399.0, 401.0 [M+H]+, 421.1, 423.0 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((4-fluorobenzylidene)amino)-4H-[1,2,4]triazole-3-
thiol (Compound 9k): White solid; yield: 94.6%; mp: 203–204 ◦C; 1H NMR (DMSO-d6)
δ/ppm: 14.54 (s, 1H, –SH), 13.31 (s, 1H, –NH), 9.49 (s, 1H, –N CH–), 8.06 (dd, J1 =
6.0 Hz, J2 = 8.4 Hz, 2H, Ph–H), 7.66 (d, J = 8.0 Hz, 1H, Ph–H), 7.58 (d, J = 8.0 Hz,
1H, Ph–H), 7.45 (t, J = 8.8 Hz, 2H, Ph–H), 7.33 (t, J = 7.6 Hz, 1H, Ph–H), 7.22

1574
J. ZHENG ET AL.
(t, J = 8.2 Hz, 1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 167.9, 163.6, 163.4, 141.4,
139.4, 138.4, 131.7, 128.7, 122.5, 116.5, 112.5; FT-IR (KBr) ν/cm−1: 3405, 2418, 1602,
1585, 1510, 1475, 1151, 834, 745; ESI-MS m/z: 339.1 [M+H]+, 361.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((4-chlorobenzylidene)amino)-4H-[1,2,4]triazole-3-
thiol (Compound 9l): Yellow solid; yield: 89.9%; mp: 153–159 ◦C; 1H NMR (DMSO-d6)
δ/ppm: 14.54 (s, 1H, –SH), 13.32 (s, 1H, –NH), 9.53 (s, 1H, –N CH–), 8.01 (d, J =
8.4 Hz, 2H, Ph–H), 7.68 (d, J = 8.4 Hz, 2H, Ph–H), 7.44 (m, 1H, Ph–H), 7.33 (t, J =
7.6 Hz, 1H, Ph–H), 7.24 (t, 1H, J = 8.4 Hz, Ph–H), 7.22 (t, J = 8.4 Hz, 1H, Ph–H); 13
C
NMR (DMSO-d6) δ/ppm: 166.0, 163.8, 141.8, 141.1, 138.8, 138.1, 131.3, 131.2, 129.8,
123.0, 111.8; FT-IR (KBr) ν/cm−1: 3385, 3251, 2415, 1657, 1593, 1564, 1531, 1488, 827,
745; ESI-MS m/z: 355.1 [M+H]+, 389.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((2,4-dichlorobenzylidene)amino)-4H-◦[1,2,4]triaz-
1
ole-3-thiol (Compound 9m): Yellow solid; yield: 94.0%; mp: 167–169 C; H NMR
(DMSO-d6) δ/ppm: 14.54 (s, 1H, –SH), 13.29 (s, 1H, –NH), 10.17 (s, 1H, –N CH–), 8.25
(d, J = 8.4 Hz, 1H, Ph–H), 7.90 (s, 1H, Ph–H), 7.69 (m, 3H, Ph–H), 7.33 (d, J = 6.8 Hz,
1H, Ph–H), 7.28 (d, J = 7.6 Hz, 1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 163.5, 161.7,
142.2, 139.3, 138.7, 136.5, 134.7, 130.2, 130.1, 129.2, 128.8, 121.1, 112.6; FT-IR (KBr)
ν/cm−1: 3399, 3132, 2361, 1649, 1587, 1555, 1513, 1489, 864, 825, 737; ESI-MS m/z:
389.1 [M+H]+, 411.1 [M+Na]+; HR-MS: calcd for C16H11Cl2N6S [M+H]+ 389.0143,
found 389.0144.
5-(1H-Benzimidazol-2-yl)-4-((4-nitrobenzylidene)amino)-4H-[1,2,4]triazole-3-
1
thiol (Compound 9n): Red brown solid; yield: 95.6%; mp: 198–199 ◦C; H NMR
(DMSO-d6) δ/ppm: 14.63 (s, 1H, –SH), 13.36 (s, 1H, –NH), 9.80 (s, 1H, –N CH–), 8.42
(d, J = 8.4 Hz, 2H, Ph–H), 8.25 (d, J = 8.4 Hz, 2H, Ph–H), 7.67 (d, J = 7.6 Hz, 1H,
Ph–H), 7.58 (t, J = 7.6 Hz, 1H, Ph–H), 7.33 (t, 1H, J = 7.6 Hz, Ph–H), 7.25 (t, J = 7.4 Hz,
1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 166.4, 163.8, 150.1, 141.9, 139.4, 138.7, 138.2,
128.2, 124.7, 124.5, 111.8; FT-IR (KBr) ν/cm−1: 3396, 2361, 1646, 1516, 1476, 1341,
846, 749; ESI-MS m/z: 366.1 [M+H]+, 388.1 [M+Na]+; HR-MS: calcd for C16H12N7O2S
[M+H]+ 366.0773, found 366.0771.
5-(1H-Benzimidazol-2-yl)-4-((3-nitrobenzylidene)amino)-4H-[1,2,4]triazole-3-
◦
1
thiol (Compound 9o): Light yellow solid; yield: 87.3%; mp: 186–187 C; H NMR
(DMSO-d6) δ/ppm: 14.63 (s, 1H, –SH), 13.38 (s, 1H, –NH), 9.79 (s, 1H, –N CH–), 8.81
(s, 1H, Ph–H), 8.49 (d, J = 8.4 Hz, 1H, Ph–H), 8.42 (d, J = 8.0 Hz, 1H, Ph–H), 7.90 (t,
J = 8.0 Hz, 1H, Ph–H), 7.67 (t, J = 8.4 Hz, 1H, Ph–H), 7.58 (t, 1H, J = 8.0 Hz, Ph–H),
7.34 (t, J = 7.6 Hz, 1H, Ph–H), 7.25 (t, J = 7.6 Hz, 1H, Ph–H); 13C NMR (DMSO-d6)
δ/ppm: 166.6, 163.8, 148.7, 143.2, 139.5, 138.7, 135.4, 134.1, 131.3, 127.4, 123.7, 121.7,
111.7; FT-IR (KBr) ν/cm−1: 3377, 3269, 2361, 1648, 1618, 1535, 1487, 1335, 806, 769,
692; ESI-MS m/z: 366.1 [M+H]+, 388.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-(benzylideneamino)-4H-[1,2,4]triazole-3-thiol
(Compound 9p): Light yellow solid; yield: 90.4%; mp: 197–199 ◦C; 1H NMR (DMSO-d6)
δ/ppm: 14.55 (s, 1H, –SH), 13.32 (s, 1H, –NH), 9.49 (s, 1H, –N CH–), 7.98 (d, J =
7.2 Hz, 2H, Ph–H), 7.67 (m, 2H, Ph–H), 7.61 (d, J = 7.6 Hz, 2H, Ph–H), 7.34 (m, 2H,
Ph–H), 7.24 (t, J = 7.6 Hz, 1H, Ph–H); 13C NMR (DMSO-d6) δ/ppm: 165.9, 163.9, 141.9,
141.2, 138.8, 133.4, 132.4, 129.6, 129.4, 124.0, 111.9; FT-IR (KBr) ν/cm−1: 3378, 3269,
2362, 1648, 1597, 1572, 1482, 746, 723; ESI-MS m/z: 321.2 [M+H]+, 343.1 [M+Na]+.
5-(1H-Benzimidazol-2-yl)-4-((1-naphthalzylidene)amino)-4H-[1,2,4]triazole-3-
◦
1
thiol (Compound 9q): Light yellow solid; yield: 86.7%; mp: 234–235 C; H NMR
(DMSO-d6) δ/ppm: 14.60 (s, 1H, –SH), 13.42 (s, 1H, –NH), 10.16 (s, 1H, –N CH–),

NITROGEN HETEROCYCLIC DERIVATIVES
1575
9.05 (d, J = 8.0 Hz, 1H, Ph–H), 8.24 (d, J = 8.4 Hz, 1H, Ph–H), 8.20 (d, J = 7.2 Hz,
1H, Ph–H), 8.09 (t, J = 4.8 Hz, 1H, Ph–H), 7.71 (m, 4H, Ph–H), 7.60 (d, J = 8.0 Hz,
1H, Ph–H), 7.34 (t, J = 7.4 Hz, 1H, Ph–H), 7.26 (t, J = 7.8 Hz, 1H, Ph–H); 13C NMR
(DMSO-d6) δ/ppm: 168.2, 163.9, 144.4, 141.8, 139.8, 133.9, 133.7, 131.2, 130.8, 129.3,
128.4, 128.3, 127.2, 126.0, 125.4, 123.8, 112.6; FT-IR (KBr) ν/cm−1: 3383, 3230, 2410,
1651, 1604, 1574, 1516, 1467, 745; ESI-MS m/z: 371.1 [M+H]+, 393.1 [M+Na]+.
REFERENCES
1. Narasimhan, B.; Sharma, D.; Kumar, P. Med. Chem. Res. 2012, 21(3), 269-283.
2. Patel, R. V.; Patel, P. K.; Kumari, P.; Rajani, D. P.; Chikhalia, K. H. Eur. J. Med. Chem. 2012,
53, 41-51.
3. Mavrova, A. T.; Wesselinova, D.; Vassilev, N.; Tsenov, J. A. Eur. J. Med. Chem. 2011, 46,
3362-3367.
4. Tonelli, M.; Simone, M.; Tasso, B.; Novelli, F.; Boido, V.; Sparatore, F.; Paglietti, G.; Pricl, S.;
Giliberti, G.; Blois, S.; Ibba, C.; Sanna, G.; Loddo, R.; La Colla, P. Bioorg. Med. Chem. 2010,
18(8), 2937-2953.
5. Kaushik, D.; Khan, S. A.; Chawla, G. Med. Chem. Res. 2012, 21(4), 459-467.
6. Kazimierczuk, Z.; Andrzejewska, M.; Kaustova, J.; Klimesˇova, V. Eur. J. Med. Chem. 2005, 40,
203-208.
7. Hazelton, J. C.; Iddon, B.; Suschitzky, H.; Woolley Ley, H. Tetrahedron 1995, 51, 10771-10794.
8. Sahoo, P. K.; Sharma, R.; Pattanayak, P. Med. Chem. Res. 2010, 19, 127-135.
9. Gupta, A. K.; Prachand, S.; Patel, A.; Jain, S. Int. J. Pharm. & Life Sci. 2012, 3, 1848-1857.
10. Demirbas, N.; Ugurluoglu, R.; Demirbas, A. Bioorg. Med. Chem. 2002, 10, 3717-3723.
11. Upmanyu, N.; Gupta, J. K.; Shah, K.; Mishra, P. J. Pharm. Biomed. Anal. 2011, 3, 259-265.
12. Almasirad, A.; Shafiee, A.; Abdollahi, M.; Noeparast, A.; Shahrokhinejad, N.; Vousooghi, N.;
Tabatabai, S. A.; Khorasani, R. Med. Chem. Res. 2011, 20(4), 435-442.
13. Aniket, K.; Mrunmayee, P. T.; Vithal, M. K.; Shweta, D.; Vilasrao, K. Int. J. Chem. Tech. Res.
2009, 1, 696-701.
14. Todoulou, O. G.; Papadakivaliraki, A. E.; Ikeda, S.; Declercq, E. Eur. J. Med. Chem. 1994, 29,
611-620.
15. Al-Soud, Y. A. Phosphorus Sulfur Silicon Relat. Elem. 2008, 183, 2021-2036.
16. Kane, J. M.; Dudley, M. W.; Sorensen, S. M.; Miller, F. P. J. Med. Chem. 1988, 31, 1253-1258.
17. Joseph, J.; Nagashri, K. Appl. Biochem. Biotechnol. 2012, 167, 1446-1458.
18. Alam, M. S.; Choi, J.-H.; Lee, D.-U. Bio. Med. Chem. 2012, 20, 4103-4108.
19. Jhaumeer-Laulloo, S.; Bhowon, M. G.; Mungur, S.; Maho-moodally, M. F.; Subratty, A. H. Med.
Chem. 2012, 8, 409-414.
20. Al-Masoudi, N. A.; Aziz, N. M.; Mohammed, A. T. Phosphorus Sulfur Silicon Relat. Elem.
2009, 184, 2891-2901.
21. Cansız, A.; Koparır, M.; Demirdag˘, A. Molecules 2004, 9, 204-212.
22. Hu, G. Q.; Dong, X. L.; Xie, S. Q.; Huang, W. L. Acta Pharm. Sinica. 2008, 43, 50-53.
23. Thakurdesai, P. A.; Wadodkar, S. G.; Chopade, C. T. Pharmacologyonline. 2007, 1, 314-329.
24. Sabri, S. S.; El-Abadelah, M. M.; Yasin, H. A. J. Heterocycl. Chem. 1987, 24, 165-169.