Triarylimidazo[1,2-a]pyridine-8-carbonitriles: solvent-free synthesis and their anti-cancer evaluation

Article abstract of DOI:10.1080/00397911.2019.1605445

In this study, we have presented the synthesis of novel 2,5,7-triarylimidazo[1,2-a]pyridine-8-carbonitriles from 2-amino-4,6-diarlypyridine-3-carbonitrile and nitrostyrene using FeCl₃ (20 mol%) as Lewis acid under solvent-free conditions. A library of compounds with diverse substitutions have also been synthesized and screened for in-vitro anti-cancer activity against various cell lines such as A549 (Lung), HCT-116 (Colon), SW-620 (Colon), and MIAPACA (Pancreas).

Full text of DOI:10.1080/00397911.2019.1605445

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Triarylimidazo[1,2-a]pyridine-8-carbonitriles:
solvent-free synthesis and their anti-cancer
evaluation
Annah Gupta, Sonakshi Sasan, Avneet Kour, Nargis Nelofar, Dilip Manikrao
Mondhe & Kamal K. Kapoor
To cite this article: Annah Gupta, Sonakshi Sasan, Avneet Kour, Nargis Nelofar, Dilip
Manikrao Mondhe & Kamal K. Kapoor (2019): Triarylimidazo[1,2-a]pyridine-8-carbonitriles:
solvent-free synthesis and their anti-cancer evaluation, Synthetic Communications, DOI:
10.1080/00397911.2019.1605445
To link to this article: https://doi.org/10.1080/00397911.2019.1605445
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https://doi.org/10.1080/00397911.2019.1605445
Triarylimidazo[1,2-a]pyridine-8-carbonitriles: solvent-free
synthesis and their anti-cancer evaluation
Annah Guptaa, Sonakshi Sasana, Avneet Kourb, Nargis Nelofarc, Dilip Manikrao
Mondheb, and Kamal K. Kapoora
b
aDepartment of Chemistry, University of Jammu, Jammu, India; Cancer Pharmacology Division, CSIR-
c
Indian Institute of Integrative Medicines, Jammu, India; Department of Zoology, G.D.C, Jammu, India
ABSTRACT
ARTICLE HISTORY
Received 12 January 2019
In this study, we have presented the synthesis of novel 2,5,7-triaryli-
midazo[1,2-a]pyridine-8-carbonitriles from 2-amino-4,6-diarlypyridine-
3-carbonitrile and nitrostyrene using FeCl3 (20 mol%) as Lewis acid
under solvent-free conditions. A library of compounds with diverse
substitutions have also been synthesized and screened for in-vitro
anti-cancer activity against various cell lines such as A549 (Lung),
HCT-116 (Colon), SW-620 (Colon), and MIAPACA (Pancreas).
KEYWORDS
Imidazo[1,2-a]pyridines; fer-
ric chloride; nitrostyrene;
diarlypyridine-3-carbonitrile
GRAPHICAL ABSTRACT
Introduction
Imidazopyridine represents an important class among polynitrogen containing hetero-
cycles and exhibits a plethora of biological activity. Imidazo[1,2-a]pyridine, in particular,
is one of the most significant structural unit in the area of natural products and phar-
maceuticals.[1] Despite this, it also finds its application in material science.[2,3]
Imidazo[1,2-a]pyridines display interesting biological activities over a broad range of
therapeutic classes such as antineoplastic,[4] antiviral,[5] anti-tubercular,[6] anti-inflam-
matory,[7] anti-diabetic,[8] antipyretic,[9] antihypertensive,[10] anticonvulsant,[11] anti-
bacterial,[12] CDK2 inhibitor,[13] molluscicidal,[14] and kinase inhibitor.[15] Their effects
CONTACT Kamal K. Kapoor
kamalkka@gmail.com
Department of Chemistry, University of Jammu, Jammu 180
006, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
A. GUPTA ET AL.
on neuroactive steroids[16] and inhibitory role on NO synthase[17] have also been docu-
mented. They have also been reported as GABA and benzodiazepine receptor ago-
nists,[18] b-amyloid formation inhibitors,[19] histamine H2 receptor antagonists,[20] and
cardiotonic agents.[21] Their role as inhibitors of cyclooxygenase-2 (COX-2),[22] choles-
terol acyltransferase,[23] and geranylgeranyl transferase[24] have also been reported.
Some marketed drugs such as zolpidem (used in the treatment of insomnia), alpidem
(as anxiolytic agent), olprinone (for the treatment of acute heart failure), zolimidine
(used for the treatment of peptic ulcer), necopidem and saripidem (as anxiolytic agent),
miroprofen (analgesic), and minodronic acid (for the treatment of osteoporosis) contain
imidazo[1,2-a] pyridine moiety as their core structure (Figure 1).[25] GSK812397 is
another drug which contains imidazo[1,2-a]pyridine nucleus and is used for the treat-
ment of HIV infection.[26] Rifaximin is an antibiotic, used to prevent and treat traveler’s
diarrhea,[27] and soraprazan is found to be potent inhibitor of gastric H, K-ATPase and
is used to treat gastric acid related diseases.[28]
Imidazo[1,2-a]pyridine-8-carbonitriles such as I and II have been reported as select-
ive inhibitor of mammalian osteoclast cell activity[29] and binding agents to b-amyloid
plaques.[30]
In the light of significance of imidazopyridines in medicinal chemistry and material
science, several methods for their synthesis are reported.[31–38] In continuation of our
interest in the synthesis of pyridines[39–41] and imidazopyridines,[42,43] we contemplated
the synthesis of highly functionalized imidazo[1,2-a]pyridine-8-carbonitriles of general
structure A for their anti-cancer evaluation.
Results and discussion
At the beginning of our study, 2-amino-4,6-diphenylpyridine-3-carbonitrile and (E)-(2-
nitrovinyl)benzene were chosen as model substrates and reaction was performed as per

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Figure 1. Few marketed drugs containing imidazo[1,2-a]pyridine scaffold.
the procedure (20 mol% FeCl3 as catalyst in DMF at 80 ꢀC) reported by Hajra et al.[31]
The desired product, 2,5,7-triphenylimidazo[1,2-a]pyridine-8-carbonitrile was obtained
after 15 h of reaction in 34% yield only. In order to improve the yield of the reaction
various solvents such as CHCl3, EtOH, MeOH, DCE, isopropanol, and CH3CN were
used in place of DMF, but none was found to be beneficial (Table 1, Entry 2–7). In
another experiment, the reaction was conducted without any solvent at 80 ꢀC; a mar-
ginal improvement in the yield was witnessed. Raising the temperature of solvent-free
reaction led us to realize that at 120 ꢀC, the best yield was obtained (Table 1, Entry
8–13). Replacing FeCl3 with various other catalysts such as FeSO4, Fe(NO3)3, ZnCl2,
CuSO4, SbCl3, Bi(NO3)3, as well as I2/DMSO did not result in improving the yield of

4
A. GUPTA ET AL.
Table 1. Optimization of reaction conditions.
S. No.
Catalyst
Solvent
Temperature (ꢀC)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeSO4
Fe(NO3)3
I2
DMF
CHCl3
EtOH
MeOH
DCE
iso-propanol
CH3CN
80
60
80
60
90
90
80
80
90
100
110
120
130
120
120
120
120
120
120
120
15
15
15
15
15
15
15
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
34
32
42
35
30
28
34
52
65
68
72
75
75
n.r
n.r
n.r
n.r
32
n.r
n.r
-
-
-
-
–
-
-
-
9
10
11
12
13
14
15
16
17
18
19
20
DMSO
ZnCl2
CuSO4
SbCl3
Bi(NO3)3
-
-
-
-
aIsolated yields.
Table 2. Scanning of catalyst concentration.
S. No.
FeCl3 (mol %)
Yielda (%)
1
2
3
4
5
6
10
20
30
50
100
0
23
75
75
65
57
n.r
Reaction conditions: 2-amino-4,6-diphenylpyridine-3-carbonitrile (1 mmol), (E)-(2-nitrovinyl)benzene (1 mmol) at 120 ꢀC.
aIsolated yields
the reaction (Table 1, Entry 14–20). In order to scan the amount of catalyst required,
the reaction was performed with different amounts of catalyst (10, 20, 30, 50, and
100 mol%), and it was witnessed that 20 mol% of the catalyst gave the best yield of the
product (Table 2).
Having established the optimal reaction conditions, we turned our attention toward
the scope of reaction for the synthesis of various 2,5,7-triarylimidazo[1,2-a]pyridine-8-
carbonitrile (3a–m). Various electron donating and electron withdrawing groups on 2-
amino-4,6-diarlypyridine-3-carbonitrile and 2-nitrostyrene were well tolerated in this
transformation. 2-Amino-4,6-diarlypyridine-3-carbonitrile bearing heterocyclic moiety

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also gave the desired product (3m) in good yield. With 1-nitrobutene, the reaction did
not occur and the starting material was recovered intact.
3a
3b
3c
,30 min
75%
,30 min
73%
,40 min
71%
3d
3e
3f
,45 min
,45 min
75%
,45 min
73%
73%
3g
3h
3i
,50 min
76%
,60 min
74%
,30 min
76%
3j
3k
3l
,30 min
74%
,40 min
74%
,30 min
72%
3m,45 min
73%

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A. GUPTA ET AL.
Scheme 1. Plausible mechanism for the synthesis of 2,5,7-triarylimidazo[1,2-a] pyridine-8-carbonitrile
A mechanistic rationale portraying the probable sequence of events is shown in
Scheme 1. The first step of the reaction is Michael addition of 2-amino-4,6-diarlypyri-
dine-3-carbonitrile on nitroolefins to form intermediate 4. FeCl3 increases the electro-
philicity of the nitroolefins and thus facilitate the addition of 2-amino-4,6-
diarlypyridine-3-carbonitrile. Nitro intermediate 4 tautomerises to 5, which undergoes
intramolecular cyclization followed by nitroxyl and water elimination to generate the
final product 3.
Pharmacological report on in-vitro anti-cancer activity evaluation of the
synthesized compounds
Method
The study of the anticancer activity of the synthesized molecules has been carried out at
Pharmacology Department, IIIM, Jammu. All the synthesized molecules were tested for
in vitro cytotoxicity against various human cancer cell lines. In brief, a three-day MTT
cytotoxicity assay was performed, which was based on the principle of uptake of MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), a tetrazolium salt, by the
metabolically active cells where it is metabolized by active mitochondria into a blue col-
ored formazan product that is read spectrophotometrically. MTT was dissolved in phos-
phate buffered saline with a pH of 7.4 to obtain an MTT concentration of 2.5mg/ml; the
resulting mixture was filtered through a 0.22-micron filter to sterilize and remove a small
amount of insoluble residue. The stock solution (1ꢁ 10ꢂ2 M) of the compounds was pre-
pared in dimethyl sulphoxide (DMSO) and were further diluted with growth medium
(RPMI-1640 with 2 mM glutamine, pH 7.4, 10% fetal bovine serum, 100 mg/mL strepto-
mycin, and 100 units/ml penicillin) to obtain desired concentration. The cells were grown

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Table 3. IC50 values of the synthesized compounds against some cell lines (mM).
SAMPLE
A549 (Lung)
MIA PACA (Pancreas)
SW-620 (Breast)
HCT-116 (Colon)
3a
3b
3c
3d
3e
3f
3g
3h
3i
21.23
30.43
29.78
27.56
27.99
32.90
29.53
29.62
32.71
19.52
20.03
28.99
17.49
30.41
9.27
27.43
32.55
27.41
32.57
31.68
22.31
31.50
28.01
28.90
24.09
28.77
25.94
28.05
20.89
30.56
32.66
26.71
35.55
29.70
28.53
26.52
26.84
21.83
26.93
20.11
22.55
11.21
30.55
32.46
20.76
32.79
33.57
27.51
27.39
18.43
18.64
32.95
3j
3k
3l
3m
ꢄ IC50 >10 mM indicate that the compound is not active.
ꢄ IC50 values were calculated using Prism software.
ꢄ Paclitaxel was used as positive control for A549.
ꢄ Camptothecin was used as positive control for MIA PACA.
ꢄ 5-Fluorouracil was used as positive control for SW-620 and HCT-116.
From the data, it is observed that compound 3b showed significant activity against MIAPACA cell line.
in tissue culture flasks in growth medium at 37ꢀC in an atmosphere of 5% CO2 and 95%
relative humidity in a CO2 incubator. For each type of tumor cell, 70,000–10,000 cells per
well per 100 mL were seeded in a 96-well culture plate and incubated with the individual
compounds in a CO2 incubator for a total of 24 h.
The final concentration range of compounds was 10–50mM. Control cells, not treated
with the compounds, were similarly incubated. The assay was terminated by adding 100 mg
(20 ml) of MTT to each well, then incubating for additional 4 h, and finally adding 150 ml
of DMSO to each well to lyse the cells and dissolve formazan. The plate was read spectro-
photometrically at 570 nm and the percentage of cytotoxicity calculated using the formula:
Cytotoxicity percentage ¼ 100 ꢁ ½1–X=R1Þꢃ;
where X ¼ (absorbance of treated sample at 570 nm) – (absorbance of blank at 570 nm)
and R1 ¼ absorbance of blank at 570 nm.
The IC50 values of the cytotoxicity, [the concentration at which 50% of the cells are
killed in vitro] was calculated for each cell line treated with the test compounds The
four human cancer cell-lines screened are A549 (Lung), HCT-116 (Colon), SW-620
(Colon) and MiaPaca (Pancreas).
Anti-cancer activity (in-vitro)
The results in terms of IC50 values of in-vitro cytotoxicity of the synthesized compounds
are shown in Table 3.
Experimental
General
All the experiments were performed in an oven dried glass apparatus. All the commer-
cially available reagents were purchased from Aldrich and were used without further

8
A. GUPTA ET AL.
purification. Melting points (ꢀC) were measured in open glass capillaries using Perfit
melting point apparatus and are uncorrected. The progress of reaction was monitored
using thin layer chromatography (TLC) using silica gel pre-coated aluminum sheets (60
F254, Merck). The crude products were purified using silica gel column chromatog-
raphy (petroleum ether/EtOAc).Visualization of spots was effected by exposure to
ultraviolet light (UV) at 365 nm and 254 nm, iodine vapors and 2% 2,4-dinitrophenylhy-
drazine in methanol containing few drops of H2SO4, draggendroff reagent, and anisalde-
hyde reagent. Solvents used in purification were distilled prior to use. Recrystallization
was achieved with ethanol. IR spectra (ꢀ, cmꢂ1) were recorded on Perkin–Elmer FTIR
1
spectrophotometer using KBr discs. H and 13 C NMR were recorded on Bruker AC-
1
400 spectrometer operating at 400 MHz for H and 100 MHz for 13 C with tetramethyl-
silane (TMS) as an internal standard. The chemical shifts are expressed in d (ppm)
downfield from TMS. All the 13C NMR spectra are proton decoupled. J values are given
1
in Hertz (Hz). The abbreviations s, d, dd, t, q, and m in H NMR spectra refer to sing-
let, doublet, doublet of doublet, triplet, quartet, and multiplet, respectively. Solvents
were removed using Heidolph rotary evaporator. For the HRMS measurement,
Quadrupole time of flight (QTOF) was used.
Procedure for the synthesis of 2,5,7-triphenylimidazo[1,2-a]pyridine-8-
carbonitrile (3a)
A mixture of 2-amino-4,6-diphenylpyridine-3-carbonitrile (1 mmol), 2-nitro-1-phenyl-
ethylene (1 mmol) and FeCl3 (20 mol%) was taken in 25 ml round bottomed flask and
dipped in preheated oil bath maintained at 120 ꢀC. The reaction was continued till its
completion (30 min). The resultant was column chromatographed to give the
pure product.
2,5,7-Triphenylimidazo[1,2-a]pyridine-8-carbonitrile (3a)
Yellow solid, M.P: 270–272 ꢀC. 1H NMR (400 MHz, CDCl3) d 8.00–7.99 (m, 3H),
7.78–7.72 (m, 4H), 7.69–7.63 (m, 3H), 7.58–7.51 (m, 3H), 7.43 (t, J ¼ 7.4 Hz, 2H), 7.36
(t, J ¼ 7.3 Hz, 1H), 6.96 (s, 1H). 13C NMR (100 MHz, CDCl3) d 147.6, 145.0, 141.3,
136.3, 133.1, 132.7, 130.8, 129.6, 129.0, 128.6, 128.2, 126.4, 115.5, 114.0, 107.4, 97.6. IR
(KBr, tmax cmꢂ1): 3055, 2223, 1614, 1477, 1261. HRMS (ESI): calcd. for C26H17N3
[M þ H]þ, 372.1502; found: 372.1478.
Conclusion
In conclusion, a protocol has been developed for the synthesis of novel 2,5,7-triarylimi-
dazo[1,2-a]pyridine-8-carbonitrile from readily available starting materials. The reaction
occurred in the presence of 20 mol% FeCl3 under solvent-free conditions. A library of
compounds with diverse substitutions has also been synthesized. 2,5,7-
Triarylimidazo[1,2-a]pyridine-8-carbonitrile (3 a-m) were screened for in-vitro anti-can-
cer activity against various cell lines such as A549 (Lung), HCT-116 (Colon), SW-620

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(Colon) and MIAPACA (Pancreas) and only the compound 3b showed significant activ-
ity against MIA PACA cell line.
Full experimental details, 1H and 13C NMR spectra can be found via the
“Supplementary content” section of this article’s webpage.
Acknowledgments
The authors are thankful to Department of Chemistry, University of Jammu for providing all
necessary facilities and Department of Science and Technology, Government of India, New Delhi
for NMR facility under PURSE and INSPIRE fellowship [AG].
References
[1] Koubachi, J.; Kazzouli, S. E.; Bousmina, M.; Guillaumet, G. Eur. J. Org. Chem. 2014, 2014,
5119. DOI: 10.1002/ejoc.201400065.
[2] Wan, J.; Zheng, C.-J.; Fung, M.-K.; Liu, X.-K.; Lee, C.-S.; Zhang, X.-H. J. Mater. Chem.
2012, 22, 4502. DOI: 10.1039/c2jm14904d.
[3] Chernyak, N.; Gevorgyan, V. Angew. Chem. Int. Ed. Engl. 2010, 49, 2743. DOI: 10.1002/
anie.200907291.
[4] Baviskar, A. T.; Madaan, C.; Preet, R.; Mohapatra, P.; Jain, V.; Agarwal, A.; Guchhait,
S. K.; Kundu, C. N.; Banerjee, U. C.; Bharatam, P. V. J. Med. Chem. 2011, 54, 5013. DOI:
10.1021/jm200235u.
[5] Elleder, D.; Baiga, T. J.; Russell, R. L.; Naughton, J. A.; Hughes, S. H.; Noel, J. P.; Young,
J. A. T. Virol. J. 2012, 9, 305. DOI: 10.1186/1743-422X-9-305.
[6] Odell, L. R.; Nilsson, M. T.; Gising, J.; Lagerlund, O.; Muthas, D.; Nordqvist, A.; Karl, A.;
Larhed, M. Bioorg. Med. Chem. Lett. 2009, 19, 4790. DOI: 10.1016/j.bmcl.2009.06.045.
[7] Lacerda, R. B.; de Lima, C. K. F.; da Silva, L. L.; Romeiro, N. C.; Miranda, A. L. P.;
Barreiro, E. J.; Fraga, C. A. M. Bioorg. Med. Chem. 2009, 17, 74. DOI: 10.1016/
j.bmc.2008.11.018.
[8] Narasimhan, B.; Sharma, D.; Kumar, P. Med. Chem. Res. 2011, 20, 1119. DOI: 10.1007/
s00044-010-9472-5.
[9] Almirante, L.; Polo, L.; Mugnaini, A.; Provinciali, E.; Rugarli, P.; Biancotti, A.; Gamba, A.;
Murmann, W. J. Med. Chem. 1965, 8, 305. DOI: 10.1021/jm00327a007.
[10] Laneri, S.; Di Ronza, C.; Bernardi, A.; Ostacolo, C.; Sacchi, A.; Cervone, C.; D’Amico, M.;
Di Filippo, C.; Letizia Trincavelli, M.; Panighini, A.; Martini, C. Chddt. 2011, 11, 87. DOI:
10.2174/187152911798347016.
[11] Ulloora, S.; Shabaraya, R.; Aamir, S.; Adhikari, A. V. Bioorg. Med. Chem. Lett. 2013, 23,
1502. DOI: 10.1016/j.bmcl.2012.12.035.
[12] Byth, K. F.; Culshaw, J. D.; Green, S.; Oakes, S. E.; Thomas, A. P. Bioorg. Med. Chem.
Lett. 2004, 14, 2245. DOI: 10.1016/j.bmcl.2004.02.015.
[13] Che, C.; Xiang, J.; Wang, G. X.; Fathi, R.; Quan, J. M.; Yang, Z. J. Comb. Chem. 2007, 9,
982. DOI: 10.1021/cc070058a.
[14] El Shehry, M. F.; Swellem, R. H.; Abu-Bakr, S. M.; El-Telbani, E. M. Eur. J. Med. Chem.
2010, 45, 4783. DOI: 10.1016/j.ejmech.2010.07.043.
[15] Zanze, I. A.; Wakefield, B. D.; Gasiecki, A.; Kalvin, D.; Johnson, E. F.; Kovar, P.; Djuric,
S. W. Bioorg. Med. Chem. Lett. 2011, 21, 1480. DOI: 10.1016/j.bmcl.2011.01.001.
[16] Trapani, G.; Laquintana, V.; Denora, N.; Trapani, A.; Lopedota, A.; Latrofa, A.; Franco,
M.; Serra, M.; Pisu, M. G.; Floris, I.; et al. J. Med. Chem. 2005, 48, 292. DOI: 10.1021/
jm049610q.
[17] Strub, A.; Ulrich, W.-R.; Hesslinger, C.; Eltze, M.; Fuchs, T.; Strassner, J.; Strand, S.;
Lehner, M. D.; Boer, R. Mol. Pharmacol. 2006, 69, 328. DOI: 10.1124/mol.105.017087.

10
A. GUPTA ET AL.
[18] Humphries, A. C.; Gancia, E.; Gilligan, M. T.; Goodacre, S.; Hallett, D.; Merchant, K. J.;
Thomas, S. R. Bioorg. Med. Chem. Lett. 2006, 16, 1518. DOI: 10.1016/j.bmcl.2005.12.037.
[19] Fuchs, K.; Romig, M.; Mendla, K.; Briem, H.; Fechteler, K. Chem. Abstr 2002, 2002,
183824.
[20] Kishino, H.; Moriya, M.; Sakuraba, S.; Sakamoto, T.; Takahashi, H.; Suzuki, T.; Moriya, R.;
Ito, M.; Iwaasa, H.; Takenaga, N.; et al. Bioorg. Med. Chem. Lett. 2009, 19, 4589. DOI:
10.1016/j.bmcl.2009.06.101.
[21] Davey, D.; Erhardt, P. W.; Lumma, W. C.; Jr., Wiggins, J.; Sullivan, M.; Pang, D.; Cantor,
E. J. Med. Chem. 1987, 30, 1337. DOI: 10.1021/jm00391a012.
ꢀ
[22] Almansa, C.; de Arriba, A. F.; Cavalcanti, F. L.; Gomez, L. A.; Miralles, A.; Merlos, M.;
ꢀ
Garcıa-Rafanell, J.; Forn, J. J. Med. Chem. 2001, 44, 350. DOI: 10.1021/jm0009383.
[23] Jin, Y.; Rho, M.-C.; Gajulapati, K.; Jung, H. Y.; Boovanahalli, S. K.; Lee, J. H.; Song, G.-Y.;
Choi, J. H.; Kim, Y. K.; Lee, K.; Choi, Y. Bull. Korean Chem. Soc. 2009, 30, 1297.
[24] McKenna, C. E.; Kashemirov, B. A.; Błaz_Ewska, K. M.; Mallard-Favier, I.; Stewart, C. A.;
Rojas, J.; Lundy, M. W.; Ebetino, F. H.; Baron, R. A.; Dunford, J. E.; et al. J. Med. Chem.
2010, 53, 3454. DOI: 10.1021/jm900232u.
[25] Pericherla, K.; Kaswan, P.; Pandey, K.; Kumar, A. Synthesis 2015, 47, 887. DOI: 10.1055/s-
0034-1380182.
[26] Boggs, S.; Elitzin, V. I.; Gudmundsson, K.; Martin, M. T.; Sharp, M. Org. Process Res. Dev.
2009, 13, 781. DOI: 10.1021/op9000675.
[27] Koo, H. L.; Dupont, H. L. Curr. Opin. Gastroenterol. 2010, 26, 17. DOI: 10.1097/
MOG.0b013e328333dc8d.
[28] Simon, W. A.; Herrmann, M.; Klein, T.; Shin, J. M.; Huber, R.; Senn-Bilfinger, J.; Postius,
S. J. Pharmacol. Exp. Ther. 2007, 321, 866. DOI: 10.1124/jpet.107.120428.
[29] Herslof, M.; Nordberg, P.; Sornsen, H. WO 01/25237 A1.
[30] Bario, J. R.; Petric, A. J.; Satyamurthy, N.; Kepe, V.; Small, G. W. US 20070053831 A1.
[31] Santra, S.; Bagdi, A. K.; Majee, A.; Hajra, A. Adv. Synth. Catal. 2013, 355, 1065. DOI:
10.1002/adsc.201201112.
[32] Yan, R.-L.; Yan, H.; Ma, C.; Ren, Z.-Y.; Gao, X.-A.; Huang, G.-S.; Liang, Y.-M. J. Org.
Chem. 2012, 77, 2024. DOI: 10.1021/jo202447p.
[33] Yan, H.; Yang, S.; Gao, X.; Zhou, K.; Ma, C.; Yan, R.; Huang, G. Synlett 2012, 23, 2961.
DOI: 10.1055/s-0032-1317685.
[34] Jagadhane, P. B.; Telvekar, V. N. Synlett 2014, 25, 2636. DOI: 10.1055/s-0034-1379185.
[35] Devi, E. S.; Alanthadka, A.; Nagarajan, S.; Sridharan, V.; Maheswari, C. U. Tetrahedron
Lett. 2018, 59, 3485. DOI: 10.1016/j.tetlet.2018.08.024.
[36] Pan, L.; Hang, N.; Zhang, C.; Chen, Y.; Li, S.; Sun, Y.; Li, Z.; Meng, X. Molecules 2017,
22, 213. DOI: 10.3390/molecules22020213.
[37] Balalaie, S.; Derakhshan-Panah, F.; Zolfigol, M. A.; Rominger, F. Synlett 2018, 29, 89.
DOI: 10.1055/s-0036-1590906.
[38] Ghosh, P.; Ganguly, B.; Kar, B.; Dwivedi, S.; Das, S. Synth. Commun. 2018, 48, 1076. DOI:
10.1080/00397911.2018.1434893.
[39] Gupta, A.; Kaur, R.; Singh, D.; Kapoor, K. K. Tetrahedron Lett. 2017, 58, 2583. DOI:
10.1016/j.tetlet.2017.05.067.
[40] Kour, R.; Gupta, A.; Kapoor, K. K. Res. Chem. Intermed. 2017, 43, 6099. DOI: 10.1007/
s11164-017-2979-3.
[41] Khajuria, R.; Kannaboina, P.; Kapoor, K. K.; Gupta, A.; Raina, G.; Jassal, A. K.; Rana,
L. V.; Hundal, M. S.; Das, P. Org. Biomol. Chem. 2015, 13, 5944. DOI: 10.1039/
c5ob00545k.
[42] Kour, D.; Gupta, A.; Kapoor, K. K.; Gupta, V. K.; Rajnikant, R.; Singh, D.; Das, P. Org.
Biomol. Chem. 2018, 16, 1330. DOI: 10.1039/C7OB02750H.
[43] Kour, D.; Khajuria, R.; Kapoor, K. K. Tetrahedron Lett. 2016, 57, 4464. DOI: 10.1016/
j.tetlet.2016.08.058.