Design and synthesis of novel triazole linked pyrrole derivatives as potent Mycobacterium tuberculosis inhibitors

Article abstract of DOI:10.1007/s00044-017-1997-4

This research is focused on the rational approach to design and synthesis of a novel series of triazole linked pyrrole derivatives through a sequential Paal–Knorr reaction and Click chemistry. These new molecules were screened against Mycobacterium tuberculosis H37Rv and found to display promising anti-mycobacterial activity. Among various compounds, 7g and 7l were identified as leads with minimum inhibitory concentration value 0.78 (μg/mL), which are more effective than standard drugs such as pyrazinamide, ethambutol, and ciprofloxacin and less active than isoniazid and rifampicin. These molecules (minimum inhibitory concentration values <12.5 μg/mL) were also screened against HEK-293T cancer cell lines. Most of these molecules are less toxic but possess higher selectivity index, which indicates the suitability of these compounds for further evaluation.

Full text of DOI:10.1007/s00044-017-1997-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-017-1997-4
ORIGINAL RESEARCH
Design and synthesis of novel triazole linked pyrrole derivatives as
potent Mycobacterium tuberculosis inhibitors
1 ●
2 ●
3 ●
3 ●
M. Lakshmi Devi P. Lakshmi Reddy P. Yogeeswari D. Sriram
T. Veera Reddy
1 ●
4 ●
2
B. V. Subba Reddy R. Narender
Received: 25 February 2017 / Accepted: 17 July 2017
Springer Science+Business Media, LLC 2017
©
Abstract This research is focused on the rational approach
to design and synthesis of a novel series of triazole linked
pyrrole derivatives through a sequential Paal–Knorr reac-
tion and Click chemistry. These new molecules were
screened against Mycobacterium tuberculosis H37Rv and
found to display promising anti-mycobacterial activity.
Among various compounds, 7g and 7l were identified as
leads with minimum inhibitory concentration value 0.78
selectivity index, which indicates the suitability of these
compounds for further evaluation.
●
●
Keywords Antitubercular activity Stetter reaction
●
●
Paal–Knorr synthesis Click chemistry Trisubstituted
pyrrole derivatives
(
μg/mL), which are more effective than standard drugs such
Introduction
as pyrazinamide, ethambutol, and ciprofloxacin and less
active than isoniazid and rifampicin. These molecules
Tuberculosis (TB) is a chronic infectious disease caused by
pathogenic Gram positive bacteria called Mycobacterium
tuberculosis (MTB). TB frequently attacks the lungs, but it
also affect other parts of the body (Rogoza et al. 2010). The
symptoms of pulmonary TB include chronic cough, weight
loss, intermittent fever, night sweats, and coughing blood.
The World Health Organization (WHO) estimates that one-
third of the population is infected with (MTB) annually,
there are approximately 8 million new infections and 3
million deaths are attributed to M. tuberculosis (Naresh et al.
(
minimum inhibitory concentration values <12.5 μg/mL)
were also screened against HEK-293T cancer cell lines.
Most of these molecules are less toxic but possess higher
Electronic supplementary material The online version of this article
(
doi:10.1007/s00044-017-1997-4) contains supplementary material,
which is available to authorized users.
2
010; Marriner et al. 2011). Although TB can be treated and
even cured by chemotherapy, the treatment requires
–9 months of time period that is too long, and is accom-
*
*
*
T. Veera Reddy
veerareddyt000@gmail.com
6
B. V. Subba Reddy
basireddyvsr@gmail.com
panied by a significant toxicity. More than 20 drugs are
currently used for the treatment of TB and most of them
were developed 50 years ago (Thomas et al. 2014). There-
fore, there is an urgent necessity to develop a more powerful
and faster acting anti-TB drugs with new mode of action to
overcome drug resistance, lengthy treatment duration and
toxicity, that enforce the researchers across the globe.
Pyrrole is an important nitrogen containing heterocyclic
compound, which is frequently present in a wide range of
natural products including pyrrolomycins, pyoluteorin,
pyrrolnitrin, chlorophyll, vitamins B12, and bilirubine
(Walsh et al. 2006). The biological activity of pyrrole
R. Narender
raviralanarender@gmail.com
1
2
3
4
Department of Chemistry, Vikrama Simhapuri University, Nellore
5
24001, India
Crop Protection Chemicals, Indian Institute of Chemical
Technology, Tarnaka, Hyderabad 500 007, India
Department of Pharmacy, Birla Institute of Technology &
Science-Pilani, Hyderabad Campus, India
Natural Product Chemistry, Indian Institute of Chemical
Technology, Tarnaka, Hyderabad 500 007, India

Med Chem Res
derivatives has been evaluated by various research groups
Shrinivas et al. 2014; La Regina et al. 2014). TB activity of
substituted pyrrole (BM212) was first reported by Deidda
using NaBH (Kamal et al. 2013) to give the respective
4
(
alcohols (4a–d). Bromination of the alcohols (4a–d) fol-
lowed by the treatment of bromides (5a–d) with NaN3
gave the desired azides (6a–d). 1,3-Dipolar cycloaddition
(Ackermann and Potukuchi 2010) of azides (6a–d) with
terminal alkynes afforded the desired 1,2,3-triazole linked
pyrrole derivatives (7a–x) in good yields.
et al. (1998), and its analogs were prepared by Biava et al.
(
2008). Another pyrrole derivative, LL-3858 was also found
to be active against TB, which was reported by Lupin
Limited in 2004. Currently it is in phase II clinical trials
(
Sandeep et al. 2011). The copper-catalyzed a 1,3-dipolar
cycloaddition of alkynes and azides to form 1,2,3-triazoles
is the most popular reaction in Click chemistry (Krystian
et al. 2014). 1,2,3-Triazoles are mainly used as bioisosteres
and linkers for the synthesis of bioactive compounds such
as anti-tuberculosis (Deepak et al. 2014; Boechat et al.
Biology
Antibacterial activity
All synthesized compounds were evaluated for their
anti-tubercular activity against M. tuberculosis H37Rv
2
011), anti-cancer (Jabeena et al. 2014) and antibacterial
(
Kavitha et al. 2014) antivirus and antifungal (Ramachan-
(ATCC27294) by agar dilution method (Franzblau et al. 1998).
drana et al. 2011). They were considered to be the most
useful components for the construction of complex mole-
cules (Antonino et al. 2014) such as pharmaceutical drugs
like tazobactam, carboxyamidotriazole, and cefatriazine
Isoniazid, rifampicin, ethambutol and ciprofloxacin were used
as standard drugs. The minimum inhibitory concentration
(MIC) values demonstrated as µg/mL, were determined for
each compound against test mycobacteria. Newly synthesized
compounds having MIC ≤ 12.5 µg/mL were further scrutinized
for cytotoxicity (Gerlier and Thomasset 1986) by 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
(
Fig. 1). Thus, the Click chemistry has attracted widespread
interest from virtually all areas of drug discovery. Inspired
by inherent anti-TB activity of pyrrole derivatives (Gholap
2
016) (Fig. 2) and potential use of 1,2,3-triazole ring
Rangappa et al. 2015) (Fig. 3) as bioisostere, we were
(MTT) against HEK cell line at 50 µM concentration.
(
The anti-mycobacterial activity data of all tested com-
pounds were depicted in Table 1. MTB activity of these
compounds was shown in MIC values ranging from 0.78 to
interested in the design and synthesis of triazole linked
pyrrole derivatives as new anti-TB agents
>
25 µg/mL. Among them, triazole linked pyrrole con-
jugates 7b, 7c, 7f, 7g, 7j, 7l, 7n, 7q, 7r, 7u, and 7v, dis-
played MIC values below 6.25 µg/mL. Remarkably, 7g and
Results and discussions
Chemistry
7l exhibited potent anti-TB activity (0.78 µg/mL), and in
particular, 7j showed MIC value 1.56 µg/mL and another
four compounds 7b, 7q, 7u, and 7v showed MIC value
3.125 µg/mL. When compared to first-line TB drugs for
example ethambutol (MIC 3.13 µg/mL), seven compounds
7b, 7g, 7j, 7l, 7q, 7u, and 7v were found to be more potent,
albeit they were less effective than other TB drugs including
isoniazid and rifampicin (Table 1).
Our synthetic strategy for the triazole linked pyrrole deri-
vatives (7a–x) is outlined in Scheme 1. Accordingly,
treatment of aldehyde with chalcone (1a–c) under Stetter
conditions (Reddy et al. 2012; Biava et al. 2005) provided
the corresponding 1,4-diketone (2a–d). Thus formed 1,4-
diketone (2a–d) was then treated with 1-(4-aminophenyl)
ethanone under Paal-Knorr conditions (Nicolaou and
Demopoulos 2003) to afford the corresponding 1-(4-(2,3,5-
trisubstituted-1H-pyrrol-1-yl)phenyl)ethanone (3a–d). These
compounds (3a–d) were further subjected to reduction
The structure–activity relationship of newly synthesized
triazole linked pyrrole conjugates has been investigated
with respect to standard TB drugs (isoniazid, rifampicin,
ethambutol, and ciprofloxacin). Among them, 7a–f contain R,
2
1
3
R = phenyl, R = p-chlorophenyl groups, and R = pyridine,
Fig. 1 1,2,3-Triazole containing
pharmaceutical agents
2
2
3
2
2

Med Chem Res
Fig. 2 TB active pyrrole
derivatives
3
Fig. 3 1,2,3-Triazole containing
anti-tubercular agents
2
3
7
b exhibited good activity (MIC = 3.125 µg/mL). If the
R = phenyl groups, and R = CH CH OH, 7q exhibited the
2 2
3
3
pyridine (R ) is replaced by –CH CH CH CH OH (7a) or
reasonable activity (MIC = 3.125 µg/mL), and
R
2
2
2
2
by p-tolyl (7d), the molecules displayed moderate activity
= –CH CH CH CH OH (7n) or p-tolyl (7r) displayed
2
2
2
2
3
(
MIC = 12.5 µg/mL). The presence of CH CH OH (7c) or
moderate activity (MIC = 6.25 µg/mL). If R = pyridine
(7o), or phenyl (7p) or pentylbenzene (7s) showed low
activity (MIC = 12.5 µg/mL). Compounds 7t–x contain R,
2
2
n-pentylbenzene (7f), the molecules showed improved
3
activity by two folds (MIC = 6.25 µg/mL). If R is hexyl
1
2
3
(
7
7e), the molecule displayed lower activity. Compounds
g–m contain R , R = phenyl, R = p-tolyl groups, and R
R ,
R = phenyl,
and
R = phenyl
(7u)
or
1
2
3
–CH CH CH CH OH (7v) exhibited good activity (MIC =
2
2
2
2
=
–CH OH (7g) or p-tolyl (7l) exhibited potent activity
3.125 µg/mL). If R3 = n-pentylbenzene (7x) showed low
activity (MIC = 12.5 µg/mL), and R3 = pyridine (7t) or
hexyl (7w) groups displayed least activity. The above study
indicates that the position of the substituent on pyrrole and
triazole plays a crucial role in the observed activity and the
triazole linked pyrrole derivatives were found to exhibit
promising anti-tuberculosis agents.
2
3
(
MIC = 0.78 µg/mL). If R = –CH CH OH (7j), the mole-
2
2
3
cule displayed excellent activity (MIC = 1.56 µg/mL), if R
–CH CH CH CH OH (7k), or n-pentylbenzene (7m),
=
2
2
2
2
the molecules showed moderate activity (MIC = 12.5 µg/
mL), if R = pyridine (7h) or phenyl (7i) has less effect on
the TB activity. Compounds 7n–s contain R, R2 = p-tolyl,
3

Med Chem Res
Scheme 1 Synthesis of triazole
linked pyrrole derivatives (7a–x)
The active compounds were further subjected to in vitro
cytotoxicity studies against HEK-293T cell line at 50 µg/mL
concentration (Fig. 4). Selectivity index (SI) ratio between
IC50 and MIC; if the SI > 25, the compounds were con-
sidered as nontoxic. The percentage of growth inhibition,
IC50 and selectivity index (SI) values presented in Table 2.
Compounds 7g, and 7l showed 8.954% and 18.956 inhi-
bition respectively at 50 µg/mL with selectivity index of >
screened for anti-tubercular activity against M. tuberculosis
H37Rv pathogens. Most of these compounds display
moderate to excellent anti-mycobacterial activity (25–0.78
μg/mL). Among them, two compounds (7g and 7l) display
potent anti-tubercular activity (0.78 μg/mL) with low cyto-
toxicity and high selective index. The results reported in this
study would be useful in guiding future efforts to discover
new compounds with increased tuberculosis activity.
6
4. These results imply the suitability of these compounds
in drug development for tuberculosis.
Experimental section
Chemistry protocols
Conclusion
In summary, we have synthesized a novel series of triazole
linked pyrrole conjugates employing Paal–Knorr reaction
followed by Click chemistry. These molecules were
All chemicals (Alfa Aesar and Sigma Aldrich) used possess
a purity of >95%. Yield refers to pure products after

Med Chem Res
Table 1 Synthesis and antimicrobial activity of 7a–x
1
2
3
1
2
3
Entry
R
R
R
R
MIC (µg/mL) MTB H37Rv
Entry
R
R
R
R
MIC (µg/mL)
MTB H37Rv
7
a
12.5
7m
12.5
7
b
3.125
7n
6.25
7
c
6.25
7o
12.5
7
d
12.5
7p
12.5

Med Chem Res
Table 1 continued
1
2
3
1
2
3
Entry
R
R
R
R
MIC (µg/mL) MTB H37Rv
Entry
R
R
R
R
MIC (µg/mL)
MTB H37Rv
7
e
25
7q
3.125
7
f
6.25
7r
6.25
7
g
0.78
7s
12.5
7
h
25
7t
25

Med Chem Res
Table 1 continued
1
2
3
1
2
3
Entry
R
R
R
R
MIC (µg/mL) MTB H37Rv
Entry
R
R
R
R
MIC (µg/mL)
MTB H37Rv
7
i
25
7u
3.125
7
j
1.56
7v
3.125
7
k
12.5
7w
25
7
l
0.78
7x
12.5
Rifampicin
Isoniazid
0.24
0.72
7.64
4.71
Rifampicin
Isoniazid
0.24
0.72
7.64
4.71
Ethambutol
Ethambutol
Ciprofloxacin
Ciprofloxacin

Med Chem Res
purification and are unoptimized. Melting points were
determined in open capillaries on Gallenkamp apparatus
and are uncorrected. IR spectra were recorded on a Buck
136.0 (Ar–C), 137.5 (Ar–C), 137.8 (Ar–C), 138.8 (Ar–C),
197.7 (C=O), 206.9 (C=O).
1
Scientific IR M-500 spectrophotometer in KBr pellets, H
1
3
and C nuclear magnetic resonance (NMR) spectra for
analytical purpose were recorded in CDCl3, on a Bruker
instrument at 300 and 75 MHz, respectively; chemical shifts
are expressed in δ-scale downfield from TMS as an internal
standard. High-resolution mass spectra were obtained by
using ESI-QTOF mass spectrometry. Silica gel 60 (230–400
mesh) was used for the column chromatography. Thin-layer
chromatography (TLC) plates (Silica Gel 60 F254) were
used for TLC.
General procedure for the preparation of 1,2,3,5-
tetrasubstituted pyrrolyl phenyl ethanone 3a–d
Paal-Knorr conditions: To a solution of 1,4-diketone (1
equiv) in EtOH (10 v for 1 g), was added p-TSA (1.1 equiv)
followed by 4-amino acetophenone (2 equiv). The resulting
o
mixture was stirred at 75 C for 16 h. The progress of the
reaction was monitored by TLC. After completion, the
mixture was cooled to room temperature and then con-
centrated in vacuo to get the crude compound. It was
extracted twice with EtOAc and the combined organic
layers were washed twice with water and once with brine
General procedure for synthesis of 2a–d
To a stirred solution of the bis-thiazolium salts (0.2 mmol)
solution, dried over anhydrous Na SO , filtered, and the
2 4
in 3 mL of ethanol were added 0.2 mL of Et N (2.0 mmol)
solvent was removed in vacuo. The resulting material was
purified by column chromatography to afford the desired
product.
3
and an aldehyde (1.0 mmol). The mixture was allowed to
stir for 10 min at room temperature and then chalcone (1
mmol) was added. The resulting mixture was kept under
reflux for 15 h at 70 °C.The progress of the reaction was
monitored by TLC. The mixture was quenched with water
and extracted with ethyl acetate (2 × 15 mL). Removal of
the solvent followed by purification on silica gel column
chromatography furnished the pure 1,4-diketone.
1-(4-(3-(4-Chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-yl)
phenyl)ethanone (3a)
1
Off white solid; yield: 92%; H NMR: δ 7.82 (d, 2H, J =
.3 Hz, Ar–H), 7.34 (d, 3H, J = 7.3 Hz, Ar–H), 7.29 (t, 2H,
J = 7.4 Hz, Ar–H), 7.24–7.11 (m, 10H, Ar–H), 6.71 (s, 1H,
8
2
-(4-Chlorophenyl)-1,4-diphenylbutane-1,4-dione (2a)
1
3
pyrrole–CH), 2.56 (s, 3H, O=C–CH3); C NMR: δ 26.5
(–CH ), 110.8 (pyrrole–CH), 122.0 (Ar–C), 126.2 (Ar–C),
1
Colorless oil; yield: 84%; H NMR: δ 7.93 (t, 6H, J = 3.7
Hz, Ar–H), 7.51 (t, 1H, J = 7.1 Hz, Ar–H), 7.41 (t, 2H, J =
3
126.9 (Ar–C), 127.4 (Ar–C), 127.6 (Ar–C), 128.1 (Ar–C),
128.2 (Ar–C), 128.2 (Ar–C), 128.3 (Ar–C), 128.5 (Ar–C),
128.5 (Ar–C), 128.6 (Ar–C), 128.9 (Ar–C), 132.1 (Ar–C),
133.0 (Ar–C), 133.2 (Ar–C), 135.1 (Ar–C), 135.5 (Ar–C),
136.0 (Ar–C), 136.3 (Ar–C), 138.2 (Ar–C), 142.5 (Ar–C),
142.9 (Ar–C), 197.1 (C=O).
7
(
.5 Hz, Ar–H), 7.34 (d, 1H, J = 8.3 Hz, Ar–H), 7.19–7.31
m, 4H, Ar–H), 5.20 (dd, 1H, J = 3.0, 9.8 Hz, Ar–CH–C =
O), 4.15 (dd, 1H, J = 10.5, 17.9 Hz, O=C –CH –CH–),
2
1
3
3
.22 (dd, 1H, J = 3.0, 17.9 Hz, O=C –CH –CH–);
C
2
NMR: δ 43.8 (–CH –), 48.7 (–CH–), 127.5 (Ar–C), 128.1
2
(Ar–C), 128.6 (Ar–C), 128.8 (Ar–C), 129.3 (Ar–C), 130.3
(Ar–C), 133.3 (Ar–C), 134.8 (Ar–C), 135.7 (Ar–C), 136.3
(Ar–C), 138.2 (Ar–C), 139.3 (Ar–C), 197.7 (C=O), 198.0
(C=O).
1
-(4-(2,3-Diphenyl-5-(p-tolyl)-1H-pyrrol-1-yl)phenyl)
ethanone (3b)
1
1
,2,4-Triphenylbutane-1,4-dione (2d)
White solid; yield: 84%; H NMR: δ 7.75 (d, 2H, J = 8.5
Hz, Ar–H), 7.24–7.07 (m, 10H, Ar–H), 7.03 (d, 2H, J = 8.6
Hz, Ar–H), 6.96 (d, 2H, J = 8.0 Hz, Ar–H), 6.90 (d, 2H, J
= 8.3 Hz, Ar–H), 6.71 (s, 1H, pyrrole–CH), 2.54 (s, 3H,
1
Yellow oil; yield: 89%; H NMR: δ 7.98 (t, 4H, J = 7.5 Hz,
Ar–H), 7.14–7.54 (m, 10H, Ar–H), 7.19 (d, 1H, J = 5.2 Hz,
Ar–H), 5.28 (dd, 1H, J = 6.7, 18.2 Hz, Ar–CH–C = O),
1
3
O=C–CH ), 2.28 (s, 3H, Ar–CH
(Ar–CH ), 26.5 (O=C–CH
3
); C NMR: δ 21.2
3
3
4
.17 (dd, 1H, J = 9.8, 17.9 Hz, O = C –CH –CH–), 3.24
3
), 110.7 (pyrrole–CH), 123.8
2
1
3
(
dd, 1H, J = 3.5, 17.9 Hz, O = C –CH –CH–); C NMR: δ
(Ar–C), 125.5 (Ar–C), 126.5 (Ar–C), 128.1 (Ar–C), 128.5
(Ar–C), 128.6 (Ar–C), 128.8 (Ar–C), 129.0 (Ar–C), 129.1
(Ar–C), 131.1 (Ar–C), 132.0 (Ar–C), 132.5 (Ar–C), 134.5
(Ar–C), 135.1 (Ar–C), 135.8 (Ar–C), 136.9 (Ar–C), 143.0
(Ar–C), 197.2 (C=O).
2
4
1
1
1
1.8 (–CH –), 53.4 (–CH–), 113.6 (Ar–C), 120.7 (Ar–C),
2
27.4 (Ar–C), 127.4 (Ar–C), 127.8 (Ar–C), 128.0 (Ar–C),
28.1 (Ar–C), 128.7 (Ar–C), 128.8 (Ar–C), 129.4 (Ar–C),
29.7 (Ar–C), 132.9 (Ar–C), 133.2 (Ar–C), 134.4 (Ar–C),

Med Chem Res
1
-(4-(3-Phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)phenyl)
was stirred at rt for 12 h, the residue was dissolved in DCM,
the organic phase was washed twice with water, once with
brine. The combined organic layer was dried over anhy-
drous Na SO and concentrated in vacuo. The crude com-
ethanone (3c)
1
White solid; yield: 84%; H NMR: δ 7.75 (d, 2H, J = 8.5
Hz, Ar–H), 7.20–7.06 (m, 9H, Ar–H), 7.02 (d, 2H, J = 8.6
Hz, Ar–H), 6.95 (d, 2H, J = 8.0 Hz, Ar–H), 6.90 (d, 2H, J
2
4
pound was directly used in next step.
=
8.1 Hz, Ar–H), 6.68 (s, 1H, pyrrole–CH), 2.54 (s, 3H,
General procedure for the preparation of triazole
O=C–CH ), 2.30 (s, 3H, Ar–CH ), 2.28 (s, 3H, Ar–CH );
substituted pyrroles 7a–x
3
3
3
1
3
C NMR: δ 21.0 (Ar–CH ), 21.2 (Ar–CH ), 26.5
3
3
(
(
(
(
(
(
O=C–CH ), 110.7 (pyrrole–CH), 123.7 (Ar–C), 126.5
To a solution of 1-(4-(1-azidoethyl)phenyl)-2,3,5-trisub-
3
Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.5 (Ar–C), 128.6
Ar–C), 128.7 (Ar–C), 128.8 (Ar–C), 129.0 (Ar–C), 129.2
Ar–C), 131.2 (Ar–C), 131.7 (Ar–C), 132.6 (Ar–C), 132.8
Ar–C), 133.4 (Ar–C), 135.1 (Ar–C), 136.8 (Ar–C), 143.1
Ar–C), 197.2 (C=O).
stituted-1H-pyrrole (1 equiv) in THF:H O (3:2) were added
2
CuSO (0.1 equiv), sodium ascorbate (0.05 equiv), and
4
alkyne derivative (1.1 equiv). The reaction mixture was
stirred at rt for 2 h. The reaction mixture was diluted with
ethyl acetate, the organic phase was washed twice with
water, once with brine. The organic phase was dried over
anhydrous Na SO and filtered. The solvent was removed in
General procedure for the preparation of 1,2,3,5-
2
4
tetrasubstituted pyrrolyl phenyl ethanol 4a–d
vacuo, The crude compound was purified by column
chromatography to afford the desired product with good
yield.
To a solution of 1,2,3,5-tetrasubstituted pyrrolylpheny-
lethanone (1 equiv) in MeOH and DCM (1:1), was added
NaBH (0.4 equiv) slowly at 0 °C. The resulting reaction
4-(1-(1-(4-(3-(4-chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-
yl)phenyl)ethyl)-1H-1,2,3-triazol-4-yl)butan-1-ol (7a)
4
mixture was stirred at rt for 12 h. The reaction mixture was
quenched with aq. ammonium chloride and concentrated in
vacuo. The solvent was removed in vacuo, and the residue
was dissolved in EtOAc. The organic phase was washed
twice with water and once with brine solution. The organic
phase was dried over anhydrous Na SO and filtered. The
1
White solid, mp: 137–138 °C; yield: 83%; H NMR: δ
7.27–7.21 (m, 4H, Ar–H), 7.20–7.15 (m, 4H, Ar–H),
7.12–7.04 (m, 7H, Ar–H), 6.99–6.90 (m, 4H, Ar–H), 6.61
(s, 1H, pyrrole-H), 5.77 (qt, 1H, –CH), 3.68 (t, J = 6.4 Hz,
2H, –CH OH) 2.74 (t, J = 7.6 Hz, 2H, –CH –), 1.91 (d, J
2
4
solvent was removed in vacuo and the resulting compound
was purified by column chromatography to afford the
desired product.
2
2
= 7.0 Hz, 3H, –CH3), 1.76 (qt, 2H, –CH), 1.65 (qt, 2H,
1
3
–CH); C NMR: δ 21.1 (CH –), 25.2 (–CH –), 25.4
3
2
(
–CH –), 32.0 (C–CH –), 59.2 (–CH –OH), 62.2 (–CH–),
2 2 2
General procedure for the preparation of 1-(4-(1-
bromoethyl)phenyl)-2,3,5-trisubstituted-1H-pyrrole
110.3 (Pyrrole-CH), 119.1 (Ar–C), 124.1 (Ar–C), 125.7
(Ar–C), 126.6 (Ar–C), 126.7 (Ar–C), 127.9 (Ar–C), 128.1
(Ar–C), 128.5 (Ar–C), 129.4 (Ar–C), 130.4 (Ar–C)), 130.8
5
a–d
(Ar–C), 132.4 (Ar–C), 132.5 (Ar–C),132.9 (Ar–C), 135.1
To a solution of 1,2,3,5-tetrasubstituted pyrrolylpheny-
lethanol (1 equiv) in ether (10 v for 1 g) was added PBr3
(Ar–C), 135.5 (Ar–C), 138.6 (Ar–C), 139.0 (Ar–C), 148.0
(Ar–C); IR (KBr): υ 758, 1092, 1211, 1483, 1600, 2934,
3063 cm ; Electrospray Ionization Mass Spectrometry
−1
(
0.3 equiv) slowly at 0 °C. The resulting mixture was stirred
at rt for 1 h. The reaction was quenched with aq. KBr and
extracted with ethyl acetate. The organic phase was washed
twice with water, once with brine solution. The organic
phase was dried over anhydrous Na SO and filtered. The
(ESI-MS): m/z: 559 [M + H].
3-(1-(1-(4-(3-(4-chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-
yl)phenyl)ethyl)-1H-1,2,3-triazol-4-yl)pyridine (7b)
2
4
solvent was removed in vacuo to get crude, which was
directly used in the next step.
1
White solid, m.p. 220–222 °C; yield: 89%; H NMR: δ 8.60
(d, J = 4.7, 1H, Pyridine-H), 8.19 (d, J = 7.9 Hz, 1H, pyr-
General procedure for the preparation of 1-(4-(1-
azidoethyl)phenyl)-2,3,5-trisubstituted-1H-pyrrole 6a–d
idine-H), 7.97 (s, 1H, pyridine-H), 7.78 (t, J = 5.9 Hz, 1H,
pyridine-H), 7.26–7.11 (m, 13H, Ar–H), 7.08–7.05 (m, 2H,
Ar–H), 6.99–6.96 (m, 2H, Ar–H), 6.92–6.89 (m, 2 H), 6.69
(s, 1H, pyrrole–H), 5.88 (qt, 1H, –CH–), 1.98 (d, J = 7.1,
To a solution of 1-(4-(1-bromoethyl)phenyl)-2,3,5-trisub-
stituted-1H-pyrrole (1 equiv) in DCM:water (1:1), was
added sodium azide (1.5 equiv) followed by a catalytic
amount of TBAB (0.1eq.). The resulting reaction mixture
1
3
3H, –CH3); C NMR: δ 21.1 (CH –), 59.5 (–CH–), 110.3
3
(Pyrrole-CH), 118.0 (Ar–C), 124.1 (Ar–C), 125.5 (Ar–C),
125.7 (Ar–C), 126.6 (Ar–C), 126.8 (Ar–C), 127.9 (Ar–C),

Med Chem Res
1
1
1
1
1
5
28.1 (Ar–C), 128.2 (Ar–C), 128.5 (Ar–C), 128.9 (Ar–C),
29.5 (Ar–C), 130.4 (Ar–C), 130.4 (Ar–C), 130.8 (Ar–C),
32.4 (Ar–C), 132.5 (Ar–C), 133.0 (Ar–C), 135.1 (Ar–C),
35.5 (Ar–C), 138.8 (Ar–C), 147.7(Ar–C); IR (KBr): υ 758,
091, 1179, 1484, 1601, 2921, 3057 cm ; ESI-MS: m/z:
78 [M + H].
(–CH–), 110.2 (pyrrole-CH), 119.0 (Ar–C), 123.4 (Ar–C),
125.5 (Ar–C), 126.4 (Ar–C), 126.6 (Ar–C), 127.9 (Ar–C),
128.1 (Ar–C), 128.6 (Ar–C), 128.6 (Ar–C), 129.3 (Ar–C),
129.5 (Ar–C), 131.2 (Ar–C), 132.7 (Ar–C), 134.6 (Ar–C),
136.0 (Ar–C), 136.7 (Ar–C), 138.7(Ar–C), 139.0(Ar–C); IR
−
1
−1
(KBr): υ 758, 1039, 1207, 1484, 1601, 2925, 3058 cm
;
+
ESI-MS: m/z: 585 [M + H] ; High-resolution mass spectra
(HRMS) (ESI) calcd for C H N Cl, 585.27895 [M +
2
-(1-(1-(4-(3-(4-Chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-
3
8 38 4
+
yl)phenyl)ethyl)-1H-1,2,3-triazol-4-yl)ethanol (7c)
H] , found 585.27900.
1
White solid, m.p. 209–211 °C; yield: 87%; H NMR:
δ7.25–7.20 (m, 4H, Ar–H), 7.19–7.15 (m, 5H, Ar–H),
1
-(1-(4-(3-(4-Chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-yl)
phenyl)ethyl)-4-(4-pentylphenyl)-1H-1,2,3-triazole (7f)
7
.12–7.05 (m, 6H, Ar–H), 6.98 (s, 1H, triazole–H), 6.93 (t,
J = 8.3 Hz, 3H, Ar–H) 6.67 (s, 1H, pyrrole– H), 5.77 (qt, J,
1
White solid, m.p. 196–198 °C; yield: 92%; H NMR: δ 7.71
1
5
H, –CH), 3.95 (t, J = 5.2 Hz, 2H, –CH OH), 2.94 (t, J =
2
1
3
(d, J = 7.9 Hz, 2H, Ar–H), 7.48 (s, 1H, triazole-H),
.2 Hz, 2H, –CH –), 1.92 (d, J = 6.7 Hz, 3H, –CH );
C
2
3
7
7
6
5
.28–7.20 (m, 6H, Ar–H), 7.19–7.14 (m, 5H, Ar–H),
.13–7.06 (m, 5H, Ar–H), 6.90 (d, J = 8.3 Hz, 2H, Ar–H),
.89 (d, J = 8.3 Hz, 2H, Ar–H), 6.67 (s, 1H, pyrrole-H),
NMR: δ 21.1 (CH –), 28.6 (–CH –), 59.4 (–CH –OH), 61.5
3
2
2
(
–CH–), 110.3 (pyrrole-CH), 120.0 (Ar–C), 124.1 (Ar–C),
1
1
1
1
1
1
25.8 (Ar–C), 126.6 (Ar–C), 126.7 (Ar–C), 127.9 (Ar–C),
28.1 (Ar–C), 128.1 (Ar–C), 128.2 (Ar–C), 128.5 (Ar–C),
29.5 (Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 132.4 (Ar–C),
32.5 (Ar–C), 132.9 (Ar–C), 135.1 (Ar–C), 135.5 (Ar–C),
38.7 (Ar–C), 138.8 (Ar–C); IR (KBr): υ 759, 1046, 1207,
.84 (qt, 1H, –CH), 2.63 (t, J = 7.5 Hz, 2H, –CH –), 1.97
2
(
1
d, J = 6.9 Hz, 3H, –CH ), 1.67–1.57 (m, 4H, –CH –),
3
2
.37–1.28 (m, 2H, –CH), 0.89 (t, J = 6.6 Hz, 3H, –CH3);
1
3
C NMR: δ 14.0 (CH –CH –), 21.1 (CH –CH–), 22.5
(–CH –), 31.0 (–CH –), 31.4 (–CH –), 35.6 (–CH –), 59.4
2 2 2 2
–CH–), 110.3 (pyrrole-CH), 117.7 (Ar–C), 124.1 (Ar–C),
3
2
3
484, 1602, 2929, 3057 cm− ; ESI-MS: m/z: 545 [M + H].
1
(
125.5 (Ar–C), 125.7 (Ar–C), 126.6 (Ar–C), 126.8 (Ar–C),
127.8 (Ar–C), 128.0 (Ar–C), 128.2 (Ar–C), 128.6 (Ar–C),
128.8 (Ar–C), 129.5 (Ar–C), 130.5 (Ar–C), 130.8 (Ar–C),
1
-(1-(4-(3-(4-Chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-yl)
phenyl)ethyl)-4-p-tolyl-1H-1,2,3-triazole (7d)
1
132.4 (Ar–C), 132.5 (Ar–C), 133.0(Ar–C), 135.2(Ar–C),
White solid, m.p. 185–187 °C; yield: 95%; H NMR: δ
.76–7.52 (m, 4H, Ar–H), 7.51–7.04 (m, 19H, Ar–H), 6.69
s, 1H, pyrrole–H), 5.87 (qt, 1H, –CH), 2.37 (s 3H, –CH ),
1
1
35.5 (Ar–C), 138.7 (Ar–C), 138.9 (Ar–C), 143.1(Ar–C),
47.9 (Ar–C); IR (KBr): υ 758, 1092, 1224, 1483, 1601,
7
(
3
−
1
1
3
2926, 3026 cm ; ESI-MS: m/z: 647 [M + H].
2
.02 (d, J = 7.0 Hz, 3H, –CH3);
C NMR: δ 21.2
(
CH –CH–), 21.3 (Ar–CH ), 59.6 (–CH–), 109.1 (pyrrole-
3 3
CH), 117.8 (Ar–C), 120.6 (Ar–C), 125.1 (Ar–C), 125.5
(
(
(
(
(
(
3
Ar–C), 125.8 (Ar–C), 125.9 (Ar–C), 126.7 (Ar–C), 127.2
Ar–C), 127.6 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.1
Ar–C), 128.3, (Ar–C), 128.6 (Ar–C), 128.9 (Ar–C), 129.4
Ar–C), 132.4 (Ar–C), 134.7 (Ar–C), 134.9 (Ar–C), 138.0
Ar–C), 138.3 (Ar–C), 140.3 (Ar–C), 142.4 (Ar–C), 147.9
Ar–C); IR (KBr): υ 759, 1074, 1226, 1451, 1603, 2922,
(1-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
ethyl)-1H-1,2,3-triazol-4-yl)methanol (7g)
1
White solid, m.p. 93–95 °C; yield: 87%; H NMR: δ 7.29
(s, 1H, triazole-H), 7.26–7.11 (m, 8H, Ar–H), 7.09–7.04 (m,
4H, Ar–H), 6.98 (d, J = 8.3 Hz 2H, Ar–H), 6.94(d, J = 7.9
Hz, 2H, Ar–H), 6.88 (d, J = 8.0, 2 H), 6.69 (s, 1H, pyrrole-
−1
030 cm ; ESI-MS: m/z: 591 [M + H].
H), 5.78 (qt, 1H, –OH), 4.77 (s, 2H, –CH –), 2.28 (s, 3H,
2
3
1
1
-(1-(4-(3-(4-Chlorophenyl)-2,5-diphenyl-1H-pyrrol-1-yl)
–CH ), 1.91 (d, J = 7.1 Hz, 3H, –CH3); C NMR: δ 21.2
3
phenyl)ethyl)-4-hexyl-1H-1,2,3-triazole (7e)
(CH –CH–), 21.2 (CH –Ar), 56.4 (–CH –OH), 59.6
3
3
2
(
–CH–), 110.1 (pyrrole-CH), 120.2 (Ar–C), 123.4 (Ar–C),
1
White solid, m.p. 180–181 °C; yield: 90%; H NMR: δ
125.4 (Ar–C), 126.4 (Ar–C), 126.6 (Ar–C), 127.9 (Ar–C),
128.0 (Ar–C), 128.5 (Ar–C), 128.6 (Ar–C), 129.2 (Ar–C),
129.5 (Ar–C), 131.1 (Ar–C), 132.0 (Ar–C), 132.6
(Ar–C),134.5 (Ar–C), 135.9 (Ar–C), 136.7 (Ar–C), 138.1
(Ar–C), 139.1 (Ar–C), 147.5 (Ar–C); IR (KBr): υ 759,
1031, 1211, 1486, 1601, 2921, 3030 cm ; ESI-MS: m/z:
510 [M + H] ; HRMS (ESI) calcd for C H ON ,
511.24924 [M + H] , found: 511.24870.
7
3
2
–
–
.29–7.01 (m, 16H, Ar–H, triazole-H), 6.94 (t, J = 10.7 Hz,
H, Ar–H), 6.67 (s, 1H, pyrrole-H), 5.76 (qt, 1H, –CH),
.70 (t, J = 6.9 Hz, 2H, –CH ), 1.91 (d, J = 6.6 Hz, 3H,
CH ), 1.72–1.59 (m, 2H, –CH –), 1.43–1.19 (m, 6H,
CH –), 0.88 (t, J = 6.9 Hz, 3H, –CH ); C NMR: δ 14.1
CH –CH –), 21.2 (CH –CH–), 22.5 (–CH –), 25.8
–CH –), 29.0 (–CH –), 29.4 (–CH –), 31.5(–CH –), 59.2
2
3
2
1
3
−1
2
3
+
(
(
3
2
3
2
34 31
4
+
2
2
2
2

Med Chem Res
−
1
1
5
5
078, 1202, 1485, 1599, 2987, 3027 cm ; ESI-MS: m/z:
+
58 [M + H] ; HRMS (ESI) calcd for C H N ,
38 32 5
+
58.26550 [M + H] , found: 558.26564.
1-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
ethyl)-4-phenyl-1H-1,2,3--triazole (7i)
1
White solid, m.p. 150–152 °C; yield: 92%; H NMR: δ7.79
d, 2H, J = 7.7 Hz, Ar–H), 7.47 (s, 1H, triazole-H), 7.42 (t,
J = 7.6 Hz, 2H, Ar–H), 7.33 (t, J = 7.1 Hz, 1H, Ar–H),
(
7
6
1
–
.26–7.07 (m, 12H, Ar–H), 7.00 (d, 2H, J = 8.2 Hz, Ar–H),
.90 (qt, 4H, Ar–H), 6.69 (s, 1H, pyrrole-H), 5.82 (qt, J =
A = rifampicin, B = isoniazid, C = ethambutol, D = ciprofloxacin
Fig. 4 Graphical representation of anti-tubercular activity (MIC <
2.5 µg/mL) and cytotoxicity A = rifampicin, B = isoniazid, C =
ethambutol, and D = ciprofloxacin
H, –CH), 2.23 (s, 3H, –CH ) 1.96 (d, J = 7.0 Hz, 3H,
3
1
13
CH3; C NMR: δ 21.1 (CH –CH–), 21.1 (CH –Ar), 59.5
3
3
(
–CH–), 110.1 (pyrrole-CH), 118.0(Ar–C), 123.3 (Ar–C),
1
1
1
1
1
25.4 (Ar–C), 125.5 (Ar–C), 126.4 (Ar–C), 126.7 (Ar–C),
27.9 (Ar–C), 128.5 (Ar–C), 18.6(Ar–C), 128.7 (Ar–C),
29.3 (Ar–C), 129.6 (Ar–C), 130.5 (Ar–C), 131.1 (Ar–C),
32.1 (Ar–C), 132.7 (Ar–C), 134.5 (Ar–C), 135.9 (Ar–C),
Table 2 Percentage (%) of cell inhibition and selectivity index (SI)
values of triazole linked pyrrole derivatives (7a–x) against HEK-
2
93Tcell line
36.7 (Ar–C), 138.2 (Ar–C), 139.1 (Ar–C), 147.6 (Ar–C);
No
MIC (µg/mL)
% inh
IC50 approximation
SI index
−1
IR (KBr): υ 760, 1077, 1202, 1485, 1600, 2920, 3030 cm
ESI-MS: m/z: 579 [M + Na] ; HRMS (ESI) calcd for
C H N , 579.25256 [M + H] , found: 557.27041.
;
+
7
7
7
7
7
7
7
7
7
7
7
b
c
f
3.125
6.25
29.654
28.658
3.254
>50
~ 16
~ 8
+
4
1 31 4
>50
6.25
>>50
>>50
>50
~ 8
2-(1-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
g
j
0.78
8.954
~ 64.1
~ 32
~ 64.1
~ 8
ethyl)-1H-1,2,3-triazol-4-yl)ethanol (7j)
1.56
28.569
18.956
6.589
l
0.78
>50
1
White solid, m.p. 99–101 °C; yield: 85%; H NMR: δ
n
q
r
u
v
6.25
>>50
>>50
>>50
>50
7
7
1
.29–7.11 (m, 9H, Ar–H), 7.10–7.01 (m, 3H, Ar–H),
.00–6.85 (m, 7H, Ar–H), 6.68 (s, 1H, pyrrole-H), 5.75 (qt,
H, –CH), 4.12–3.77 (m, 2H, –CH OH) 2.89 (t, J = 10.1
3.125
6.25
26.584
2.564
~ 16
~ 8
2
3.125
3.125
25.463
13.568
~ 16
~ 16
Hz, 2H, –CH –), 2.27 (s, 3H, –CH ), 1.90 (d, J = 6.7 Hz,
2
3
13.568
13
3H, –CH3); C NMR: δ 21.1 (CH –CH–), 21.2 (CH –Ar),
3 3
%
inh: Percentage (%) of cell inhibition
28.6 (–CH –), 59.5 (–CH–), 61.4 (–CH –OH), 110.1 (pyr-
2 2
role-CH), 123.4 (Ar–C), 125.4 (Ar–C), 126.3 (Ar–C), 126.5
Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.6 (Ar–C), 129.2
(
3
-(1-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
(Ar–C), 129.5 (Ar–C), 131.1 (Ar–C), 132.0 (Ar–C), 132.6
(Ar–C),134.5 (Ar–C), 135.9 (Ar–C), 136.7 (Ar–C), 138.3
ethyl)-1H-1,2,3-triazol-4-yl)pyridine (7h)
(
Ar–C), 139.0 (Ar–C); IR (KBr): υ 759, 1047, 1213, 1485,
1
−1
White solid, m.p. 176–178 °C; yield: 90%; H NMR: δ 8.59
s, 1H, pyridine-H), 8.19 (d, J = 2.2 Hz, 1H, pyridine-H),
.95 (s, 1H, pyridine-H), 7.79(t, J = 6.8 Hz, 1H, pyridine-
H), 7.27–7.17 (m, 8H, Ar–H), 7.15–7.07 (m, 5H, Ar–H),
1600, 2921, 3348 cm ; ESI-MS: m/z: 525 [M + H];
HRMS (ESI) calcd for C H ON Cl, 525.26672 [M +
H] , found: 525.26429.
(
7
3
4
38
2
+
6
1
1
2
.99–6.93 (m, 4H, Ar–H), 6.87 (d, J = 7.7 Hz, 2 H), 6.69 (s,
4-(1-(1-(4-(2,3-diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
ethyl)-1H-1,2,3-triazol-4-yl)butan-1-ol (7k)
H, pyrrole-H), 5.87 (qt, 1H, –CH–), 2.22 (s, 3H, –CH ),
3
1
3
.97(d, J = 6.7 Hz, 3 H); C NMR: δ 21.1 (CH –CH–),
3
1
1.2 (CH –Ar), 59.5 (–CH–), 110.1 (pyrrole–CH), 117.7
White solid, m.p. 90–93 °C; Yield: 79%; H NMR: δ
3
(Ar–C), 123.4 (Ar–C), 125.4 (Ar–C), 126.4 (Ar–C), 126.7
(Ar–C), 127.7 (Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.5
(Ar–C), 128.6 (Ar–C), 129.3 (Ar–C), 129.4 (Ar–C), 129.6
(Ar–C), 131.2 (Ar–C), 132.1(Ar–C), 132.7 (Ar–C), 134.6
(Ar–C), 135.9 (Ar–C), 136.7 (Ar–C), 137.9 (Ar–C), 138.3
(Ar–C), 139.1 (Ar–C), 147.7 (Ar–C); IR (KBr): υ 758,
7.27–7.11 (m, 8H, Ar–H), 7.10–7.01 (m, 4H, Ar–H),
7.00–6.86 (m, 6H, Ar–H), 6.68 (s, 1H, triazole-H), 5.77 (qt,
1H, –CH), 3.68 (t, J = 6.1 Hz, 2H, –CH OH), 2.73 (t, J =
2
7.4 Hz, 2H, –CH –), 2.28 (s, 3H, –CH ), 1.89 (d, J = 7.0
2
3
Hz, 3H, –CH ), 1.75 (qt, 2H, –CH ), 1.63 (qt, 2H, –CH );
3
2
2
1
3
C NMR: δ 21.1 (CH –CH–), 21.2 (CH –Ar), 25.2
3
3

Med Chem Res
(
(
(
(
(
(
(
3
–CH –), 25.5 (–CH –), 32.1 (–CH –), 59.3 (–CH–), 62.2
HRMS (ESI) calcd for C44 H43 N4, 627.34822 [M + H],
found: 627.34851.
2
2
2
–CH –OH), 110.1 (pyrrole-CH), 123.4 (Ar–C), 125.4
2
Ar–C), 126.3 (Ar–C), 126.5 (Ar–C), 127.9 (Ar–C), 128.0
Ar–C), 128.5 (Ar–C), 128.5(Ar–C), 129.3(Ar–C), 129.5
Ar–C), 131.1 (Ar–C), 132.0 (Ar–C), 132.7 (Ar–C), 134.5
Ar–C), 135.9 (Ar–C), 136.7 (Ar–C), 138.6 (Ar–C), 138.9
Ar–C); IR (KBr): υ 759, 1041, 1212, 1485, 1600, 2935,
4-(1-(1-(4-(3-phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)phenyl)
ethyl)-1H-1,2,3-triazol-4-yl)butan-1-ol (7n)
1
White solid, m.p. 92–94 °C; yield: 88%; H NMR: δ
−1
+
052 cm ; ESI-MS: m/z: 553 [M + H] ; HRMS (ESI)
7.23–6.85 (m, 18H, Ar–H), 6.66 (s, 1H, pyrrole- H), 5.74
+
calcd for C H ON , 553.29655 [M + H] , found:
(qt, 1H, –CH), 3.68 (t, J = 5.9 Hz, 2H, –CH OH), 2.73 (t, J
3
7
37
4
2
5
53.29666.
= 6.2 Hz, 2H, –CH –), 2.29 (s, 3H, –CH ), 2.28 (s, 3H,
2
3
–
CH ) 1.89 (d, J = 5.7 Hz, 3H, –CH3), 1.76 (qt, 2H,
3
1
3
–
CH –), 1.64 (qt, 2H, –CH );
C NMR: δ 21.0
2
2
1
-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
(
(
CH –CH–), 21.1 (CH –Ar–), 21.1 (CH –Ar), 25.2
–CH –), 25.4 (–CH –), 32.0 (–CH –), 59.2 (–CH–),
2 2 2
3 3 3
ethyl)-4-p-tolyl-1H-1,2,3-triazole (7l)
6
1
1
1
1
1
1
2.1 (–CH –OH–), 110.1 (pyrrole-CH), 119.1 (Ar–C),
1
2
White solid, m.p. 185–187 °C; yield: 93%; H NMR: δ 7.68
d, J = 7.5 Hz, 2H, Ar–H), 7.43 (s, 1H, triazole-H),
.27–7.20 (m, 6H, Ar–H), 7.19–7.06 (m, 8H, Ar–H), 6.99
d, J = 8.3 Hz, 2H, Ar–H), 6.91 (qt, 4H, Ar–H), 6.69 (s, 1H,
pyrrole-H), 5.83 (qt, 1H, –CH), 2.38 (s 3H, –CH ), 2.24 (s,
23.3 (Ar–C), 126.2 (Ar–C), 126.5 (Ar–C), 127.8 (Ar–C),
28.4 (Ar–C), 128.5 (Ar–C), 128.7 (Ar–C), 129.4 (Ar–C),
31.1 (Ar–C), 131.8 (Ar–C), 132.7 (Ar–C), 132.9 (Ar–C),
34.4 (Ar–C), 134.9 (Ar–C), 136.5 (Ar–C), 138.5 (Ar–C),
(
7
(
3
39.0 (Ar–C), 147.9 (Ar–C); IR (KBr): υ 762, 1077, 1263,
3
6
(
H, –CH ), 1.96 (d, J = 6.7 Hz, 3H, –CH ), 1.92 (d, J =
3 3
3
−1
491, 1599, 2919, 3031 cm
; ESI-MS: m/z: 567
1
.7 Hz, 2H, –CH3); C NMR: δ 21.0 (CH –CH–), 21.1
3
+
[M + H] .
CH –Ar), 21.2 (CH –Ar), 59.5 (–CH–), 110.1(pyrrole-
3 3
CH), 117.7 (Ar–C), 123.3 (Ar–C), 125.4 (Ar–C), 126.3
3
-(1-(1-(4-(3-Phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)phenyl)
(
(
(
(
Ar–C), 126.7 (Ar–C), 127.9 (Ar–C), 128.5 (Ar–C), 128.5
Ar–C), 128.8 (Ar–C), 129.4 (Ar–C), 129.6 (Ar–C), 131.1
Ar–C), 131.8 (Ar–C), 132.7 (Ar–C), 132.9 (Ar–C), 134.4
Ar–C), 134.9 (Ar–C), 136.6 (Ar–C), 137.9 (Ar–C), 138.2
Ar–C), 139.2 (Ar–C), 147.7 (Ar–C); IR (KBr): υ 757,
ethyl)-1H-1,2,3-triazol-4-yl)pyridine (7o)
1
White solid, mp: 179–181 °C; yield: 91%; H NMR: δ 8.59
d, J = 4.5 Hz, 1H, Pyridine-H), 8.19 (d, J = 7.5 Hz 1H,
Pyridine-H), 7.96 (s, 1H, Pyridine-H), 7.79(t, J = 14.4 Hz,
H, Pyridine-H), 7.28–6.84 (m, 18H, Ar–H), 6.67 (s, 1H,
Pyrrole-H), 5.87 (qt, 1H, –CH–), 2.30 (s, 3H, –CH ), 2.22
(
(
−
1
1
5
5
077, 1225, 1485, 1601, 2921, 3028 cm ; ESI-MS: m/z:
1
+
93 [M + Na] ; HRMS (ESI) calcd for C42 H33 N4Na,
+
3
93.26874 [M + Na] , found: 593.26866.
1
3
(
(
s, 3H, –CH ), 1.96(d, J = 7.5, 3 H); C NMR: δ 21.0
CH –CH–), 21.1 (CH –Ar), 21.1 (CH –Ar), 59.6 (–CH–),
3
3
3
3
1
-(1-(4-(2,3-Diphenyl-5-p-tolyl-1H-pyrrol-1-yl)phenyl)
110.1 (pyrrole-CH), 120.1 (Ar–C),120.6 (Ar–C), 122.8
(Ar–C), 123.3 (Ar–C), 126.3 (Ar–C), 126.6 (Ar–C), 127.9
ethyl)-4-(4-pentylphenyl)-1H-1,2,3-triazole (7m)
(
Ar–C), 128.0 (Ar–C), 128.5 (Ar–C), 128.8 (Ar–C), 129.3
1
White solid, mp: 128–131 °C; yield: 90%; H NMR: δ 7.69
(
(Ar–C), 129.5 (Ar–C), 131.1 (Ar–C), 131.8 (Ar–C), 132.6
(Ar–C), 133.0 (Ar–C), 134.4 (Ar–C), 134.9 (Ar–C), 136.6
(Ar–C), 136.9 (Ar–C), 138.0 (Ar–C), 139.2 (Ar–C), 148.2
(Ar–C), 149.2(Ar–C), 150.1 (Ar–C); IR (KBr): υ 760, 1080,
1213, 1491, 1516, 2919, 3050 cm ; ESI-MS: m/z: 572
[M + H] ; HRMS (ESI) calcd for C39 H34 N5, 572.28174
d, J = 8.3 Hz, 2H, Ar–H), 7.43 (s, 1H, triazole-H)
7
6
1
–
–
–
2
3
.28–7.06 (m, 14H, Ar–H), 6.98 (d, J = 8.4 Hz, 2H, Ar–H),
.95–6.86 (m, 4H, Ar–H), 6.69 (s, 1H, Pyrrole- H), 5.81 (qt,
H, –CH), 2.63 (t, J = 7.7 Hz, 2H, –CH2–), 2.24 (s 3H,
CH ), 1.96 (d, J = 6.9 Hz, 3H, –CH3), 1.69–1.58 (m, 2H,
CH –),1.37–1.24 (m, 4H, –CH –), 0.89 (t, J = 6.7 Hz, 3H,
CH3); C NMR: δ 13.9 (CH –CH–), 21.0 (CH –CH–),
1.1 (CH –Ar), 22.4 (–CH –), 31.0 (–CH –), 31.3 (–CH –),
5.6 (–CH –), 59.5 (–CH–), 110.1 (pyrrole-CH), 117.7
−
1
+
3
+
[M + H] , found: 572.28183.
2
2
1
3
3
3
4-Phenyl-1-(1-(4-(3-phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)
phenyl)ethyl)-1H-1,2,3-triazole (7p)
3
2
2
2
2
(
(
(
(
(
(
Ar–C), 123.4 (Ar–C), 125.4 (Ar–C), 126.4 (Ar–C), 126.6
Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.5 (Ar–C), 128.6
Ar–C), 129.3 (Ar–C), 129.6 (Ar–C), 131.1 (Ar–C), 132.1
Ar–C), 132.7, (Ar–C), 134.6 (Ar–C), 134.6 (Ar–C), 135.9
Ar–C), 136.7 (Ar–C), 138.4 (Ar–C), 139.1 (Ar–C), 143.0
1
White solid, m.p. 180–182 °C; yield: 94%; H NMR: δ7.71
(d, J = 7.3 Hz, 2H, Ar–H), 7.39 (s, 1H, triazole-H), 7.34 (t,
J = 7.5 Hz, 1H, Ar–H), 7.26 (d, J = 7.1 Hz, 1 H), 7.08–6.98
(m, 10H, Ar–H), 6.92(t, J = 8.1 Hz, 4H, Ar–H), 6.85–6.79
(m, 4H, Ar–H), 6.59 (s, 1H, pyrrole- H), 5.74 (qt, 1H,
–CH), 2.21 (s, 3H, –CH ), 2.16 (s, 3H, –CH ), 1.88 (d, J =
Ar–C), 147.7 (Ar–C); IR (KBr): υ 757, 1074, 1215, 1485,
600, 2853, 2924 cm− ; ESI-MS: m/z: 627 [M + H];
1
1
3
3

Med Chem Res
1
3
6
(
.9 Hz, 3H, –CH3; C NMR: δ 21.1(CH –CH–), 21.1
4-(4-Pentylphenyl)-1-(1-(4-(3-phenyl-2,5-di-p-tolyl-1H-
pyrrol-1-yl)phenyl)ethyl)-1H-1,2,3-triazole (7s)
3
CH –Ar), 59.5 (–CH–), 110.1 (pyrrole-CH), 118.0 (Ar–C),
3
123.4 (Ar–C), 125.4 (Ar–C), 125.5 (Ar–C), 126.4 (Ar–C),
126.7 (Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.1 (Ar–C),
128.5 (Ar–C), 128.6 (Ar–C), 128.7 (Ar–C), 129.3 (Ar–C),
129.6 (Ar–C), 130.5 (Ar–C), 131.1 (Ar–C), 132.1 (Ar–C),
132.7 (Ar–C), 134.5 (Ar–C), 135.9 (Ar–C), 136.7 (Ar–C),
138.2 (Ar–C), 139.1 (Ar–C), 147.6 (Ar–C); IR (KBr): υ
7
62, 1077, 1273, 1599, 1657, 2986, 3031 cm−1; ESI-MS:
1
White solid, mp: 137–139 °C; yield: 89%; H NMR: δ 7.70
(d, J = 8.3 Hz, 2H, Ar–H), 7.43 (s, 1H, triazole-H), 7.24 (d,
J = 8.3 Hz, 2H, Ar–H), 7.19–7.06 (m, 10H, Ar–H),
7.05–6.96 (m, 3H, Ar–H), 6.90 (qt, 4H, Ar–H), 6.67 (s, 1H,
Pyrrole- H), 5.82 (qt, 1H, –CH), 2.63, (t, 2H, –CH ), 2.30
(s, 3H, –CH ), 2.24 (s, 3H, –CH ), 1.96 (d, J = 7.5 Hz, 3H,
2
3
3
m/z: 571 [M + H]; HRMS (ESI) calcd for C H N ,
–CH3), 1.70–1.55 (m, 4H, –CH –), 1.41–1.28 (m, 2H,
4
0
35
4
2
1
3
5
71.28623 [M + H], found: 571.28620.
–CH2–), 0.89(s, 3H, –CH3);
C
NMR:
δ
13.9
(
(
(
(
(
CH –CH –), 21.0 (CH –CH–), 21.0 (CH –Ar), 21.1
3
2
3
3
CH –Ar), 22.4 (–CH –), 31.0 (–CH –), 31.3 (–CH –), 35.6
3
2
2
2
–CH –), 59.4 (CH –CH–), 110.1 (pyrrole-CH), 117.7
2
3
2
-(1-(1-(4-(3-Phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)phenyl)
Ar–C), 123.3 (Ar–C), 125.4 (Ar–C), 126.3 (Ar–C), 126.6
Ar–C), 127.9 (Ar–C), 128.5 (Ar–C), 128.8 (Ar–C), 129.4
ethyl)-1H-1,2,3-triazol-4-yl)ethanol (7q)
1
(Ar–C), 129.6 (Ar–C), 131.1 (Ar–C), 131.8 (Ar–C), 132.7
White solid, m.p. 90–92 °C; yield: 83%; H NMR: δ
.62–6.75 (m, 18H, Ar–H), 6.67 (s, 1H, pyrrole- H), 5.76
qt, 1H, –CH), 4.24–3.72(m, 1H, CH OH), 2.91 (t, J = 3.9
(
(
(
Ar–C), 132.9 (Ar–C), 134.4 (Ar–C), 134.9 (Ar–C), 136.6
Ar–C), 138.2 (Ar–C), 139.1(Ar–C), 143.0 (Ar–C), 147.7
7
(
2
Ar–C); IR (KBr): υ 760, 1080, 1213, 1490, 1598, 2919,
Hz, 2H, –CH ) 2.27, (s, 6H, –CH ), 1.91 (d, J = 6.2 Hz, 3H,
2
3
−1
1
3
3048 cm ; ESI-MS: m/z: 641 [M + H]; HRMS (ESI) calcd
for C45 H45 N4, 641.36558 [M + H], found: 641.36568.
–
CH3); C NMR: δ 21.0 (CH –CH–), 21.1 (CH –Ar), 21.2
3 3
(
CH –Ar), 29.6 (–CH –), 59.7 (–CH–), 61.4 (–CH –OH),
3 2 2
1
10.1 (pyrrole-CH), 123.3 (Ar–C), 126.3 (Ar–C), 126.5
3
1
-(1-(1-(4-(2,3,5-Triphenyl-1H-pyrrol-1-yl)phenyl)ethyl)-
H-1,2,3-triazol-4-yl)pyridine (7t)
(
(
(
(
(
Ar–C), 127.8 (Ar–C), 128.5 (Ar–C), 128.5 (Ar–C), 128.8
Ar–C), 129.3 (Ar–C), 129.5 (Ar–C), 131.1 (Ar–C), 131.8
Ar–C), 132.7 (Ar–C), 132.9 (Ar–C), 134.4 (Ar–C), 134.9
Ar–C), 136.6 (Ar–C), 138.2 (Ar–C), 139.1 (Ar–C); IR
1
White solid, m.p. 130–132 °C; yield: 88%; H NMR: δ 8.58
(d, J = 4.5 Hz, 1H, pyridine-H), 8.18 (d, J = 7.1 Hz, 1H,
pyridine-H), 7.95 (s, 1H, pyridine-H), 7.77 (t, 1H, pyridine-
H), 7.28–7.05 (m, 17H, Ar–H), 7.04–6.95 (m, 3H, Ar–H),
6
6
−1
KBr): υ 760, 1069, 1239, 1484, 1657, 2987, 3048 cm
;
ESI-MS: m/z: 538 [M + H]; HRMS (ESI) calcd for C36
H ON , 539.28054 [M + H], found: 539.28002.
3
5
4
.70 (s, 1H, pyrrole- H), 5.86 (qt, 1H, –CH), 1.96 (d, J =
1
3
.7 Hz, 3H, –CH3); C NMR: δ 21.1 (CH –CH–), 59.6
3
(
–CH–), 110.1 (pyrrole-CH), 120.1 (Ar–C), 120.6 (Ar–C),
1
-(1-(4-(3-Phenyl-2,5-di-p-tolyl-1H-pyrrol-1-yl)phenyl)
1
1
1
1
1
1
7
22.8 (Ar–C), 123.6 (Ar–C), 125.5 (Ar–C), 126.5 (Ar–C),
26.6 (Ar–C), 127.1 (Ar–C), 127.9 (Ar–C), 128.0 (Ar–C),
28.0 (Ar–C), 128.5 (Ar–C), 129.5 (Ar–C), 131.3 (Ar–C),
32.0 (Ar–C), 132.3 (Ar–C), 132.5 (Ar–C), 134.7(Ar–C),
35.8 (Ar–C), 136.9 (Ar–C), 138.2 (Ar–C), 139.0 (Ar–C),
48.2 (Ar–C), 149.2 (Ar–C), 150.1 (Ar–C); IR (KBr): υ
ethyl)-4-p-tolyl-1H-1,2,3-triazole (7r)
1
White solid, m.p. 203–205 °C; yield: 92%; H NMR: δ 7.60
d, J = 8.1 Hz, 2H, Ar–H), 7.36 (s, 1H, triazole-H) 7.16 (d,
J = 9.0 Hz, 2H, Ar–H), 7.08–6.98 (m, 10H, Ar–H),
.97–6.89 (m, 3H, Ar–H), 6.85–6.81 (m, 4H, Ar–H), 6.59
s, 1H, pyrrole-H), 5.74 (qt, 1H, –CH), 2.30, (s, 3H, –CH3),
(
−
1
6
(
58, 1078, 1180, 1483, 1600, 2924, 3051 cm ; ESI-MS:
m/z: 544 [M + H].
2
3
2
.22 (s, 3H, –CH ), 2.17 (s, 3H, –CH ), 1.88 (d, J = 6.9 Hz,
3 3
1
3
H, –CH3); C NMR: δ 21.0 (CH –CH–), 21.1 (CH –Ar),
3
3
4-Phenyl-1-(1-(4-(2,3,5-triphenyl-1H-pyrrol-1-yl)phenyl)
ethyl)-1H-1,2,3-triazole (7u)
1.1 (CH –Ar), 21.2 (CH –Ar), 59.5 (–CH–), 110.1 (pyr-
3
3
role-CH), 117.7 (Ar–C), 123.3 (Ar–C), 125.4 (Ar–C), 126.3
1
(
(
(
(
(
(
Ar–C), 126.7 (Ar–C), 127.7 (Ar–C), 127.9 (Ar–C), 128.5
Ar–C), 128.5 (Ar–C), 128.8 (Ar–C), 129.4 (Ar–C), 129.6
Ar–C), 131.1 (Ar–C), 131.8 (Ar–C), 132.7 (Ar–C), 132.9
Ar–C), 134.4 (Ar–C), 134.9 (Ar–C), 136.6 (Ar–C), 137.9
Ar–C), 138.2 (Ar–C), 139.2 (Ar–C), 147.7 (Ar–C); IR
White solid, m.p. 161–164 °C; yield: 92%; H NMR: δ 7.79
(
=
7
(
d, J = 7.1 Hz,2H, Ar–H), 7.46 (s, 1H, triazole-H) 7.43 (t, J
7.7 Hz, 2H, Ar–H), 7.34 (t, J = 7.4 Hz, 1H, Ar–H),
.26–7.09 (m, 15H, Ar–H), 7.08–6.99 (m, 4H, Ar–H), 6.70
s, 1H, pyrrole-H), 5.82 (qt, 1H, –CH), 1.97 (d, J = 7.0 Hz,
−1
1
3
KBr): υ 695, 1076, 1224, 1491, 1599, 2919, 3023 cm
;
3
1
(
H, –CH3); C NMR: δ 21.1 (CH –CH–), 59.5 (–CH–),
3
ESI-MS: m/z: 585 [M + H]; HRMS (ESI) calcd for C41
H37 N4, 585.30127 [M + H], found: 585.30227.
10.1 (pyrrole-CH), 118.1 (Ar–C), 123.6 (Ar–C), 125.5
Ar–C), 126.5 (Ar–C), 126.7 (Ar–C), 127.1 (Ar–C), 127.8

Med Chem Res
(
(
(
(
(
3
Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.1 (Ar–C), 128.5
Ar–C), 128.7 (Ar–C), 129.6 (Ar–C), 130.5 (Ar–C), 131.4
Ar–C), 132.0 (Ar–C), 132.4 (Ar–C), 132.6 (Ar–C), 134.7
Ar–C), 135.8 (Ar–C), 138.4 (Ar–C), 139.1 (Ar–C), 147.6
Ar–C); IR (KBr): υ 758, 1029, 1207, 1484, 1598, 2936,
6.70 (s, 1H, pyrrole-H), 5.80 (qt, 1H,–CH), 2.63 (t, J = 7.6
Hz, 2H, –CH –), 1.95 (d, J = 7.1 Hz, 3H, –CH ), 1.74–1.59
2
3
(m, 2H, –CH –), 1.37–1.26 (m, 4H, –CH –CH –), 0.89 (t,
2
2
2
1
3
J = 6.7 Hz, 3H, CH3); C NMR: δ 14.0 (CH –CH –), 21.1
3
2
(CH –CH–), 22.4 (–CH –), 31.0 (–CH –), 31.4 (–CH –),
3
2
2
2
−1
051 cm ; ESI-MS: m/z: 543 [M + H].
35.6 (–CH –), 59.4 (–CH–), 110.1 (pyrrole-CH), 117.7
2
(Ar–C), 123.6 (Ar–C), 125.4 (Ar–C), 125.5 (Ar–C), 126.4
4
1
-(1-(1-(4-(2,3,5-triphenyl-1H-pyrrol-1-yl)phenyl)ethyl)-
H-1,2,3-triazol-4-yl)butan-1-ol (7v)
(Ar–C), 126.6 (Ar–C), 127.0 (Ar–C), 127.8 (Ar–C), 127.9
(Ar–C), 128.0 (Ar–C), 128.5 (Ar–C), 128.8 (Ar–C), 129.5
(
Ar–C), 131.4(Ar–C), 132.0 (Ar–C), 132.4 (Ar–C), 132.6
1
White solid, m.p. 94–96 °C; yield: 82%; H NMR: δ
7
(
(Ar–C), 134.7 (Ar–C), 135.8 (Ar–C), 139.0 (Ar–C), 143.0
(Ar–C), 147.7 (Ar–C); IR (KBr): υ 758, 1076, 1225, 1484,
1599, 2925, 3051 cm ; ESI-MS: m/z: 613 [M + H].
.29–7.06 (m, 14H, Ar–H), 7.04–6.94 (m, 6H, Ar–H), 6.70
s, 1H, pyrrole- H), 5.73 (qt, J = 6.9 Hz, 1H, –CH), 3.68 (t,
J = 5.9 Hz, 2H, –CH OH), 2.73 (t, J = 7.3 Hz, 2H, –CH –),
−
1
2
2
1
.88 (d, J = 6.7 Hz, 3H, –CH ), 1.74 (qt, 2H, –CH), 1.64,
3
Acknowledgements Authors are thankful to Dr. Lakshmi Kantham,
Director and Dr. V. Jayathirtha Rao, Head, Crop Protection Chemicals
Division, CSIR-IICT, Hyderabad, INDIA for their continuous
encouragement, support and also P.L.R. thankful to UGC, New Delhi,
India for the financial support in the form of fellowships.
1
3
(
qt, 2H,–CH); C NMR: δ 21.1 (CH –CH–), 25.2 (–CH –),
3 2
2
5.4 (–CH –), 32.0 (–CH –), 59.2 (–CH–), 62.2
2 2
(
–CH –OH), 110.1 (pyrrole-CH), 119.1 (Ar–C), 123.0
2
(
(
(
(
Ar–C), 125.5 (Ar–C), 126.4 (Ar–C), 126.5 (Ar–C), 127.0
Ar–C), 127.8 (Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.5
Ar–C), 129.4 (Ar–C), 131.3 (Ar–C), 132.0 (Ar–C), 132.3
Ar–C), 132.6 (Ar–C), 134.7 (Ar–C), 135.7 (Ar–C), 138.6
Ar–C), 138.8 (Ar–C), 147.9 (Ar–C); IR (KBr): υ 758,
Compliance with ethical standards
Conflict of interest The authors declare that they have no competing
interests.
(
−
1
1
5
040, 1212, 1484, 1600, 2935, 3054 cm ; ESI-MS: m/z:
25 [M + H].
4
-Hexyl-1-(1-(4-(2,3,5-triphenyl-1H-pyrrol-1-yl)phenyl)
References
ethyl)-1H-1,2,3-triazole (7w)
Ackermann L, Potukuchi HK (2010) Regioselective syntheses of fully-
substituted 1,2,3-triazoles: the CuAAC/C–H bond functionaliza-
tion nexus. Org Biomol Chem 8:4503–4513
Antonino L, Riccardo D, Francesco M, Alessio T, Annamaria M,
Giampaolo B, Anna Maria A (2014) 1,2,3-Triazole in hetero-
cyclic compounds, endowed with biological activity, through 1,3-
dipolar cycloadditions. Eur J Org Chem 16:3289–3306
Bellina F, Rossi R (2006) Synthesis and biological activity of pyrrole,
pyrroline and pyrrolidine derivatives with two aryl groups on
adjacent positions. Tetrahedron 62:7213–7256
1
White solid, m.p. 115–117 °C; yield: 88%; H NMR: δ 7.23
t, J = 6.7 Hz, 2H, Ar–H), 7.19–7.09 (m, 10H, Ar–H),
7
(
.06–6.93 (m, 8H, Ar–H), 6.70 (s, 1H, pyrrole- H), 5.75 (qt,
H, –CH), 2.68 (t, J = 7.5 Hz, 2H, –CH –), 1.88 (d, J = 7.5
Hz, 3H, –CH ), 1.63 (t, J = 7. 5 Hz, 2H, –CH –),1.41–1.24
1
2
3
2
1
3
(
(
m, 6H, –CH ), 0.87 (t, J = 13.4 Hz, 3H, –CH ); C NMR:
2
3
75 MHz, CDCl ): δ 14.0 (CH –CH –), 21.1 (CH –CH–),
3 3 2 3
2
3
2.5 (–CH –), 25.7 (–CH –), 28.9 (–CH –), 29.3 (–CH –),
Biava M, Porretta GC, Cappelli A, Vomero S, Manetti F, Botta M,
Sautebin L, Rossi A, Makovec F, Anzini M (2005) 1,5-dia-
rylpyrrole-3-acetic acids and esters as novel classes of potent and
highly selective cyclooxygenase-2 inhibitors. J Med Chem
2
2
2
2
1.5 (–CH –), 59.2 (–CH–), 110.1 (pyrrole-CH), 118.9
2
(
(
(
(
Ar–C), 123.6 (Ar–C), 125.5 (Ar–C), 126.4 (Ar–C), 126.5
Ar–C), 127.8 (Ar–C), 127.9 (Ar–C), 128.0 (Ar–C), 128.5
Ar–C), 129.4 (Ar–C), 131.3 (Ar–C), 132.0 (Ar–C), 132.4
Ar–C), 132.6 (Ar–C), 134.7 (Ar–C), 135.8 (Ar–C), 138.8
Ar–C), 138.8 (Ar–C), 148.4 (Ar–C); IR (KBr): υ 757,
4
8:3428–343
Biava M, Porretta GC, Poce G, De Logu A, Saddi M, Meleddu R,
Manetti F, De Rossi E, Botta M (2008) 1,5-diphenylpyrrole
derivatives as antimycobacterial agents. Probing the influence on
antimycobacterial activity of lipophilic substituents at the phenyl
rings. J Med Chem 51:3644–3648
Boechat N, Ferreira VF, Ferreira SB, Ferreira MdeLG, da Silva FdeC,
Bastos MM, Costa MdosS, Lourenço MCS, Pinto AC, Krettli
AU, Aguiar A, Caroline Teixeira BM, da Silva NV, Martins PRC,
Bezerra FAFM, Camilo ALS, da Silva GP, Costa Carolina CP
(
−
1
1
5
5
068, 1212, 1484, 1599, 2926, 3053 cm ; ESI-MS: m/z:
+
51 [M + H] ; HRMS (ESI) calcd for C H N ,
3
8 39 4
+
51.31733 [M + H] , found: 551.31692.
4
-(4-Pentylphenyl)-1-(1-(4-(2,3,5-triphenyl-1H-pyrrol-1-yl)
(2011) Novel 1,2,3-triazole derivatives for use against myco-
phenyl)ethyl)-1H-1,2,3-triazole (7x)
bacterium tuberculosis H37Rv (ATCC 27294) strain. J Med
Chem 54:5988–5999
1
Deepak KB, Garima K, Saqib K, Anil KT, Ramandeep S, Diwan SR
White solid, m.p. 193–195 °C; yield: 87%; H NMR: δ 7.69
d, J = 8.0 Hz, 2H, Ar–H), 7.42 (s, 1H, triazole-
H),7.26–7.08 (m, 17H, Ar–H), 7.04–6.98 (m, 4H, Ar–H),
(2014) Synthesis of novel 1,2,3-triazole derivatives of isoniazid
(
and their in vitro and in vivo antimycobacterial activity evalua-
tion. Eur J Med Chem 81:301–313

Med Chem Res
Deidda D, Lampis G, Fioravanti R, Biava M, Porretta GC, Zanett S,
Pompei R (1998) Bactericidal activities of the pyrrole derivative
BM212 against multidrug-resistant and intramacrophagic myco-
bacterium tuberculosis strains. Antimicrob Agents Chemother
Marriner GA, Nayyar A, Eugene U, Wong SY, Mukherjee T, Via LE,
Carroll M, Edwards RL, Gruber TD, Choi I, Lee J, Arora K,
England KD, Boshoff HIM, Barry CE (2011) The medicinal
chemistry of tuberculosis chemotherapy. Top Med Chem
7:47–124
4
2:3035–3037
Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G,
Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson
RM, Gilman RH (1998) Rapid, low-technology MIC determi-
nation with clinical mycobacterium tuberculosis isolates by using
the microplate alamar blue assay. J Clin Microbiol 36:362–366
Gerlier D, Thomasset N (1986) Use of MTT colorimetric assay to
measure cell activation. Immunol Methods 94:57–63
Jabeena K, Irfan H, Laxmi Gayatri J, Leela Prasad Y, Naresh N,
Gousia C, Ajay M, Saxenab AK, Alamc MS, Qazic GN, Sampath
Kumar HM (2014) Design and synthesis of novel 1,2,3-triazole
derivatives of coronopilin as anti-cancer compounds. Eur J Med
Chem 82:255–262
Ji L, Zhou GQ, Qian C, Chen XZ (2014) Synthesis of 1,2,3-triazoles
from azide-derivatised aminocyclitols by catalytic diazo transfer
and CuAAC click chemistry. Eur J Org Chem 2:3622–3636
Kamal A, Hussaini SMA, Faazil S, Poornachandra Y, Narender Reddy
G, Ganesh Kumar C, Vikrant Singh R, Rani C, Rashmi S, Khan
IA, Jagadeesh Babu N (2013) Anti-tubercular agents. Part 8:
synthesis, antibacterial and antitubercular activity of 5-nitrofuran
based 1,2,3-triazoles. Bioorg Med Chem Lett 23:6842–6846
Kavitha M, Suresh Kumar G, Amanda LH, Elizabeth SM, Minjia Z,
Nagendra Rao S, Deviprasad RG, Barbara JM, Joanna BG,
Gregory DC, Ian JG, Lizbeth H (2014) Repurposing cryptos-
poridium inosine 5′-monophosphate dehydrogenase inhibitors as
potential antibacterial agents. ACS Med Chem Lett 5:846–850
Krystian P, Katarzyna K, Joanna D, Piotr P (2014) Structure and
evaluation of antibacterial and antitubercular properties of new
basic and heterocyclic 3-formylrifamycin SV derivatives obtained
via ‘click chemistry’ approach. Eur J Med Chem 84:651–676
La Regina G, Bai R, Coluccia A, Famiglini V, Pelliccia S, Passacantilli
S, Mazzoccoli C, Ruggier V, Sisinni L, Bolognesi A, Rensen
WM, Miele A, Nalli M, Alfonsi R, Di Marcotullio L, Gulino A,
Brancale A, Novellino E, Dondio G, Vultaggio S, Varasi M,
Mercurio C, Hamel E, Lavia P, Silvestri R (2014) New pyrrole
derivatives with potent tubulin polymerization inhibiting activity
as anticancer agents including hedgehog-dependent cancer. J Med
Chem 57:6531–6552
Naresh S, Moni S, Chauhan PMS (2010) Recent advances in the
design and synthesis of heterocycles as antitubercular agents.
Future Med Chem 2:1469–1500
Nicolaou L, Demopoulos VJ (2003) Substituted pyrrol-1-ylacetic acids
that combine aldose reductase enzyme inhibitory activity and
ability to prevent the nonenzymatic irreversible modification of
proteins from monosaccharides. J Med Chem 46:417–426
Ramachandrana R, Rania M, Senthana S, Jeong YT, Kabilana S
(2011) Synthesis, spectral, crystal structure and in vitro anti-
microbial evaluation of imidazole/benzotriazole substituted
piperidin-4-one derivatives. Eur J Med Chem 46:1926–1934
Rangappa SK, Siddappa AP, Srinivasa B, Bhari MN (2015) Triazole: a
promising antituburcular agent. Chem Biol Drug Des 86:410–423
Reddy PL, Kumar KP, Satyanarayana S, Narender R, Reddy BVS
(2012) An efficient synthesis of 2-aryl-1,4-diketones via hydro-
acylation of enones. Tetrahedron Lett 53:1546–1549
Rogoza LN, Salakhutdinov NF, Tolstikov GA (2010) Antituberculosis
activity of natural and synthetic compounds. Chem Sustain Dev
18:343–375
Sandeep G, Mona S, Kumar GM, Kapil N, Raman G (2011) New drug
regimens for old disease tuberculosis: a review. Int J Res Ayurv
Pharm 2:126–131
Shrinivas DJ, Uttam AM, Sheshagiri RD, Haresh HK, Tejraj MA,
Aravind MB (2014) Synthesis, characterization, biological
activity, and 3D-QSAR studies on some novel class of pyrrole
derivatives as antitubercular agents. Med Chem Res
23:1123–1147
Gholap SS (2016) Pyrrole: an emerging scaffold for construction of
valuable therapeutic agents. Eur J Med Chem 110:13–31
Thomas B, George D, Jyoti H (2014) Synthesis of pharmaceutically
important 1,3,4-thiadiazole derivatives as antimicrobials. Res Rev
J Chem 3:50–53
Walsh CT, Garneau-Tsodikova S, Howard-Jones AR (2006) Biolo-
gical formation of pyrroles: nature’s logic and enzymatic
machinery. Nat Prod Rep 23:517–531
World Health Organization (2014) Global tuberculosis report (2014)
WHO/HTM/TB/2014.08: WHO