Synthesis of some novel benzofuran-2-yl(4,5-dihyro-3,5-substituted diphenylpyrazol-1-yl) methanones and studies on the antiproliferative effects and reversal of multidrug resistance of human MDR1-gene transfected mouse lymphoma cells in vitro

Article abstract of DOI:10.1016/j.ejmech.2011.02.045

A new series of benzofuran-2-yl(4,5-diydro-3,5-substituted diphenylpyrazol-1-yl) methanone derivatives 8a-x by the reaction of the benzofuran-2-carbohydrazides 7 with various chalcone derivatives 3a-x using microwave irradiation has been described. The effect of synthesized compounds 8a-v was studied against human cancer cell lines for their antiproliferative activity and reversal of multidrug resistance on human MDR1-gene transfected mouse lymphoma cells. Among the 24 compounds, the 8c and 8h showed good antiproliferative activity 8b, 8f and 8k were exhibited good MDR reversal activity. The main significance of the process is easy workup process, short reaction time and high yield of the new compounds for biological interest. However, the studies on genetically modified multidrug resistant cancer cells are costly and time consuming.

Full text of DOI:10.1016/j.ejmech.2011.02.045

European Journal of Medicinal Chemistry 46 (2011) 1942e1948
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Synthesis of some novel benzofuran-2-yl(4,5-dihyro-3,5-substituted
diphenylpyrazol-1-yl) methanones and studies on the antiproliferative effects and
reversal of multidrug resistance of human MDR1-gene transfected mouse
lymphoma cells in vitro
Shrey Parekh a, Dhairya Bhavsar a, Mahesh Savant a, Shailesh Thakrar a, Abhay Bavishi a, Manisha Parmar a,
,
Hardevsinh Vala a, Ashish Radadiya a, Nilay Pandya a, Juliana Serly b, Joseph Molnár b, Anamik Shah a
*
a Department of Chemistry, Saurashtra University, Rajkot 360005, India
b Institute of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
A new series of benzofuran-2-yl(4,5-diydro-3,5-substituted diphenylpyrazol-1-yl) methanone deriva-
tives 8aex by the reaction of the benzofuran-2-carbohydrazides 7 with various chalcone derivatives 3a
ex using microwave irradiation has been described. The effect of synthesized compounds 8aev was
studied against human cancer cell lines for their antiproliferative activity and reversal of multidrug
resistance on human MDR1-gene transfected mouse lymphoma cells. Among the 24 compounds, the 8c
and 8h showed good antiproliferative activity 8b, 8f and 8k were exhibited good MDR reversal activity.
The main significance of the process is easy workup process, short reaction time and high yield of the
new compounds for biological interest. However, the studies on genetically modified multidrug resistant
cancer cells are costly and time consuming.
Received 6 December 2010
Received in revised form
16 February 2011
Accepted 17 February 2011
Available online 23 February 2011
Keywords:
Antiproliferative activity
MDR reversal activity
Mouse lymphoma cells
Benzofuran bearing pyrazolines
Microwave irradiation
Ó 2011 Elsevier Masson SAS. All rights reserved.
1. Introduction
anticancer agents. P-gp is viewed as a therapeutic target for re-
sensitizing multidrug resistant cancer cells to anticancer agents
Nowadays, one of the main problem related with treatment of
human neoplastic diseases is the phenomenon of multidrug resis-
tance (MDR) to the many anticancer agents used in chemotherapy
[1,2], by increasing drug efflux, acquire cross-resistance to many
structurally and functionally unrelated anticancer agents, which
therefore never achieve effective intracellular concentrations [3,4].
The multidrug resistance of cancer cells is often associated with the
over expression of P-glycoprotein (P-gp). Recent studies showed
that tumor cells expressing MDR-associated protein (MRP), lung
resistant protein (LRP) and mutation of DNA topoisomerase II are
likely to be MDR [4,5]. Although several mechanisms have been
reported, MDR results mainly from the over expression of ATP-
binding cassette (ABC) transporters, such as, ABCB1 (P-glycopro-
tein, P-gp), ABCC1e7 (multidrug resistant related protein 1e7,
MRP1e7) and ABCG2 (breast cancer resistance protein, BCRP),
which pump out a enormous number of chemically dissimilar
because it is considered to be more clinically significant than the
other transporters.
Numerous structurally different drugs usedin treating avarietyof
pathological conditions having MDR-reversing properties such as
verapamil [6], trifluoperazine [7], and quinine [8]. Moreover,
benzofurans and pyrazoles [9,10] are very interesting heterocycles,
which are ubiquitous in nature and show a broad range of biological
activities. Recently, the anticancer and antiviral activities of the
natural cyclopenta[b]benzofurans [11] and 4,5-dihydropyrazole [12]
have been reported, the same as for a variety of benzofuran deriva-
tives. For example, 1-[(benzofuran-2-yl)phenylmethyl] imidazoles
(I) hada potent, reversible, non-selective aromatase-inhibitoryeffect
[13] and 2-{4-[(benzofuran-2-yl)carbonyl] piprazin-1-yl}-3-pro-
pylpyridine (II) exhibited good anti-HIV activity [14]. Moreover,
various synthetic methodologies have been described for the
synthesis of benzofuran bearing pyrazole derivatives for biological
interest [15,16].
In the fight against cancer, recognition of novel potent, less toxic
and selective anticancer agents remains one of the most vital health
problems. During the course of our ongoing interest on syntheses of
* Corresponding author. Tel.: þ91 281 2581013; fax: þ91 281 2589609.
E-mail address: anamik_shah@hotmail.com (A. Shah).
0223-5234/$ e see front matter Ó 2011 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2011.02.045

S. Parekh et al. / European Journal of Medicinal Chemistry 46 (2011) 1942e1948
1943
6. Further, the reaction of 6 with hydrazine hydrate at 0e5 ꢀC
yielded the desired benzofuran-2-carbohydrazides 7. The reaction
of 7 and 3aex in the presence of glacial acetic acid gave title
molecules 8aex under microwave irradiation and the results are
cited in Table 1 (Scheme 1).
Table 1
Synthesis of some novel benzofuran-2-yl(4,5-dihyro-3,5-substituted diphenylpyr-
azol-1-yl) methanones.
Entry
R
R1
Time (min)
Yield %
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
8q
8r
H
H
H
H
H
H
H
H
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-F
4-F
4-F
4-F
4-F
4-F
4-F
4-F
H
12
14
10
12
11
14
12
12
11
10
14
11
13
12
14
12
15
11
13
10
13
12
14
14
82
86
80
84
82
88
80
86
80
86
88
84
80
82
88
86
82
86
84
86
86
86
88
84
4-CH3
4-NO2
3,4-di-OCH3
4-F
4-Cl
2-Cl
4-OCH3
H
4-Cl
4-OCH3
4-NO2
2-Cl
3,4-di-OCH3
4-CH3
4-F
3. Biological activity on multidrug resistant cancer cells
3.1. Cell cultures
L5178Y mouse T-cell lymphoma cells (ECACC cat. no. 87111908,
U.S. FDA, Silver Spring, MD, USA) were transfected with pHa MDR1/
A retrovirus, as described previously [23,24]. The MDR1-expressing
cell line was selected by culturing the infected cells with 60 ng/ml
colchicine to maintain the expression of the MDR phenotype.
L5178Y (parental, PAR) mouse T-cell lymphoma cells and the
human mdr1-transfected subline (MDR) were cultured at 37 ꢀC in
McCoy’s 5A medium supplemented with 10% heat-inactivated
H
4-Cl
horse serum, L-glutamine and antibiotics. The mouse lymphoma
8s
8t
8u
8v
8w
8x
4-OCH3
4-N02
2-Cl
3,4-di-OCH3
4-CH3
4-F
cell lines were maintained in a 5% CO2 atmosphere at 37 ꢀC.
A2780cis cell line (ECACC cat. no. 93112517, Salisbury, UK) has
been developed by chronic exposure of the parental cisplatin-
sensitive A2780 human ovary cancer cell line to increasing
concentrations of cisplatin [25,26]. This cell line was cultured in
RPMI 1640 medium supplemented with 10% heat-inactivated foetal
bovine serum,
L-glutamine and antibiotics. In order to retain
resistance, cisplatin has to be added to the medium every 2e3
various heterocyclic molecules for biological interest, we previously
reported that dihydropyridines and dihydropyrimidines are potent
active against MDR reversal cell line in tumor cells [17e21]. In
continuation of ongoing project, we have synthesized some novel
benzofuran functionalized pyrazole derivatives using microwave
irradiation and found good active against MDR reversal in tumor
cells. Among them, few compounds were exhibited well anti-
proliferative activity.
passages in 1 mM final concentration. The A2780cis cell line was
maintained in a 5% CO2 atmosphere at 37 ꢀC.
3.2. Assay for antiproliferative effect
The effects of increasing concentrations of the drugs on cell
growth were tested in 96-well flat-bottomed microtitre plates in
one parallel. The compounds were diluted in two-steps from
2. Chemistry
a starting concentration of 50
m
g/ml in a final volume of 150
m
l, and
l of
DMSO was used as a control. A total of 6 ꢁ 103 cells in 50
m
All chalcone derivatives have been synthesized by reported
procedure using substituted aldehydes and acetophenones [22].
The reaction of salisaldehyde 5 with ethyl bromoacetate 4 in the
presence of base on reflux afforded ethyl benzofuran-2-carboxylate
medium were then added to each well, with the exception of the
medium control wells. The culture plates were further incubated at
37 ꢀC for 72 h, at the end of which 15
ml of MTT solution (thiazolyl
blue solved in PBS to a final concentration of 5 mg/ml) were added
O
R
CHO
O
a
HC
C
R
R
O
R
H
1a-c
2a-h
3a-x
CHO
OH
O
O
c
b
O
OC H
Br
6
4
R
N
5
R
O
O
O
d
HC
N
C
O
NH NH
R
H
O
7
3a-x
R
where R=H, 4-Cl, 4-F.
R =H,4-CH ,4-NO etc.
8a-x
Scheme 1. Microwave assisted synthesis of substituted benzofuran bearing pyrazoline derivatives (a) NaOH, EtOH, stirred at rt, (b) K2CO3, DMF, reflux 1.5 h, (c) NH2NH2.H2O,
0e5 ꢀC, (d) glacial acetic acid, MW.

1944
S. Parekh et al. / European Journal of Medicinal Chemistry 46 (2011) 1942e1948
to each well. After further incubation at 37 ꢀC for 4 h, 100
ml of
Table 3
Multidrug resistance reversal activity of compounds 8aex on MDR1-transfected
mouse lymphoma (MDR) cell line by measuring the amount the fluorescent dye
R123.
sodium dodecyl sulphate (SDS) solution (10%) were measured into
each well and the plates were further incubated at 37 ꢀC overnight.
The cell growth was determined by measuring the optical density
(OD) at 550 nm (ref. 630 nm) with a Multiscan EX ELISA reader
(Thermo Labsystems, Cheshire, WA, USA). Inhibition of cell growth
was determined as a percentage according to the formula:
Compound
Final cc.
FAR
18.8
Compound
Final cc.
FAR
8a
8b
8c
8d
8e
8f
20
20
20
20
20
20
20
20
20
20
20
m
m
m
m
m
m
m
m
m
m
m
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
8l
20
20
20
20
20
20
20
20
20
20
20
m
m
m
m
m
m
m
m
m
m
m
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
g/ml
12.61
6.02
7.59
8m
8n
8q
8r
8s
8t
8u
8v
8w
8x
15.18
29.9
20.06
8.34
16.1
26.77
6.77
2.9
5.87
15.82
6.96
ꢀ
ꢁ
OD treated cells ꢂ OD medium control
OD cell control ꢂ OD medium control
100 ꢂ
ꢁ 100
8.72
8g
8h
8i
8j
8k
12.58
16.94
16.22
10.52
14.56
The result described in Table 2 indicates that compounds 8c and 8h
exhibit good antiproliferative activity, when compounds 8a, 8de8g,
8j and 8n show moderate antiproliferative activity.
5.85
FAR*: Fluorescence Activity Ratio.
3.3. Assay for reversal of MDR in tumor cells
The results are from one representative flow cytometric experiment in which
1 ꢁ 104 individual cells were investigated.
The cells were adjusted to a density of 2 ꢁ 106 cells/ml, resus-
pended in serum-free McCoy’s 5A medium and distributed in
0.5 ml aliquots into Eppendorf centrifuge tubes. The tested
compounds were added at different final concentrations (2.0 and
20 mg/ml), and the samples were incubated for 10 min at room
temperature. Indicator rhodamine 123 (R123) (SigmaeAldrich Kft,
Budapest, Hungary) was added to each sample to a final concen-
4. Results and discussion
Three groups of the compounds were studied for antiproliferative
effects according to the IC50 values measured on the human MDR1-
gene transfected mouse lymphoma cell line: strong antiproliferative
effect 0 < IC50 < 10
proliferative effect 10 < IC50 < 50
antiproliferative effect where IC50 > 50
m
g/ml (10 compounds), moderate anti-
g/ml (7 compounds) and no
g/ml was found and the
m
tration of 10 mg/ml and the cells were incubated for a further
20 min at 37 ꢀC, washed twice and resuspended in 0.5 ml phos-
phate-buffered saline (PBS) for analysis. The fluorescence of the cell
population was measured with a FACStar Plus flow cytometer
(Beckton, Dickinson and Company, Franklin Lakes, NJ, USA).
Verapamil (EGIS Pharmaceuticals PLC, Budapest, Hungary) was
used as a positive control in the R123 exclusion experiments at final
m
results are cited in Table 2. Half of the compounds (12 compounds:
8a, 8cee, 8g, 8h, 8l, 8q, 8te8x) had significant MDR inhibitory effect
on MDR cells in the flow cytometric experiment measuring the
accumulation of R123 fluorescent dye with FAR values above 10
when applying the compounds in 20 mg/ml final concentration.
Other half of the compounds showed only moderate effect on
reversal of multidrug resistance with FAR values below 10.
The antiproliferative effect of the compounds was different. The
concentration of 22 mM. The percentage mean fluorescence inten-
sity was calculated for the treated MDR/PAR and A2780cis cell lines
as compared with the untreated cells. Fluorescent activity ratio
(FAR) was calculated via the following equation, on the basis of the
measured fluorescence values:
lowest IC50 value was found 4.569
mg/ml (8h) while some
compounds were ineffective even at the applied 50
mg/ml
concentration (i.e. 8r). However, it is difficult to evaluate the
connection between chemical structures and affectivity of benzo-
furan methanones. At any rate some substitutions on R1 position
increased the antiproliferative activity, because 4 (8d, 8h, 8n and
9k) of the best 10 compounds contained the functional group,
however further investigations are required to clarify the effects of
several functional groups at different positions.
The possible correlation between the FAR values and the chem-
ical structure of the compounds need some QSAR evaluation related
to rational drug design. The majority of compounds were found
good resistance modifiers according to their higher FAR values in
comparison with the positive control verapamil. Interestingly, the
MDR treated=MDR control
FAR ¼
parental treated=parental control
The results presented are obtained from a representative flow
cytometric experiment in which 1 ꢁ105 individual cells of the
population were evaluated for the amount of R123 retained are first
presented by the FACS Star Plus flow cytometer as histograms and
the data were converted to FAR units that define fluorescence
intensity, standard deviation, peak channel in the total and in the
gated populations (Table 3).
nontoxic compound 8h with the lowest IC50 value (4.569 mg/ml) was
Table 2
found to be the second most active one as MDR reversal agent with
Antiproliferative effect in IC50 value of newly synthesized compounds.
FAR value of 26.77 in the flow cytometric experiment.
Compound
IC50
(
mg/ml)
Compound
IC50 (mg/ml)
8a
8b
8c
8d
8e
8f
8g
8h
8i
7.58
16.602
4.866
6.888
9.936
5.134
6.219
4.569
13.632
8.496
5.743
8l
34.125
44.79
6.29
5. Experimental procedures
8m
8n
8q
8r
8s
8t
8u
8v
8w
8x
11.765
5.1. Materials and methods
>50
22.997
>50
45.193
>50
Melting points were determined in open capillary tubes and are
uncorrected. Formation of the compounds was routinely checked
by TLC on silica gel-G plates of 0.5 mm thickness and visualized by
iodine and UV. All the compounds were purified using Flash
chromatography. IR spectra were recorded in Shimadzu FT-IR-8400
instrument using KBr pellet method. Mass spectra were recorded
on Shimadzu GCeMS-QP-2010 model using Direct Injection Probe
technique. 1H NMR was recorded on a Bruker Ac 400 MHz spec-
trometer in DMSO-d6/CDCl3 solution. Elemental analysis of all the
8j
8k
>50
>50
The IC50 values below 10
effective, “good” while the compounds with IC50 value between 10 and 50
were classified as “moderately active” (8b, 8i, 8l, 8m, 8q, 8s and 8u). The other tested
compounds had no antiproliferative activity at the highest applied concentration,
mg/ml (8a, 8ceh, 8j, 8k and 8n) were considered as very
m
g/ml
50 mg/ml.

S. Parekh et al. / European Journal of Medicinal Chemistry 46 (2011) 1942e1948
1945
synthesized compounds was carried out using Elemental Vario EL
III Carlo Erba 1108 model and the results are in agreements with the
structures assigned.
(1H, t), 7.44 (1H, t), 7.64 (3H, m), 7.69 (1H, d, J ¼ 8.0 Hz), 7.80 (1H, d,
J ¼ 8.0 Hz), 7.88 (2H, m), 8.13 (1H, s); 13C NMR (CDCl3)
d: 39.9, 59.6,
109.0, 111.6, 120.6, 120.9, 121.0, 123.3, 124.7, 127.9, 128.7, 128.9,
129.2, 129.5, 130.5, 130.9, 131.1, 134.0, 146.4, 149.6, 150.0, 151.8,
158.4, 165.0; MS m/z ¼ 411 (Mþ); Anal. Calcd. for C24H17N3O4: C,
70.07; H, 4.16; N, 10.21; O, 15.56. Found: C, 70.04; H, 4.12; N, 10.20;
O, 15.51%.
5.2. Preparation of ethyl benzofuran-2-carboxylate 6
To the mixture of salisaldehyde (0.01 mole) and DMF (30 ml),
were added ethyl bromoacetate (0.01 mole) and K2CO3 (0.03 mole).
The reaction mixture was refluxed for 1.5 h at 100 ꢀC on oil bath. After
completionof the reaction, reactionmixturewaspouredintocrushed
ice. Then product was extracted using ethyl acetate (50 ml ꢁ 3), the
combined organic layer was washed using brine solution (20 ml ꢁ 2).
The organic layer was dried using anhydrous sodium sulphate and
the solvent evaporated under reduced pressure to acquire the
product in a viscous liquid form. Yield e 77%, bp e 276 ꢀC.
5.4.4. (Benzofuran-2-yl)(4,5-dihydro-5-(3,4-dimethoxyphenyl)-3-
phenylpyrazol-1-yl)methanone (8d)
mp e 150e154, IR (KBr, cmꢂ1): 3044, 2922, 1690, 1638, 1543,
1180, 1112, 962; 1H NMR (400 MHz)
d (ppm): 3.22 (1H, m), 3.66 (1H,
m), 3.70(6H, s), 5.83 (1H, m), 6.52 (1H, m), 6.61 (2H, m), 7.19 (2H,
m), 7.30 (3H, m), 7.49 (2H, m), 7.60 (2H, m), 7.59 (1H, s); 13C NMR
(CDCl3) d: 39.9, 56.2, 56.6, 59.9, 109.0, 111.6, 112.0, 115.1, 120.3, 121.0,
123.3, 124.7, 128.6, 128.9, 129.2, 129.5, 130.5, 131.1, 134.0, 136.8,
147.8, 149.6, 150.0, 151.8, 158.4, 165.0; MS m/z ¼ 426 (Mþ); Anal.
Calcd. for C26H22N2O4: C, 73.23; H, 5.20; N, 6.57; O, 15.01. Found: C,
73.22; H, 5.20; N, 6.51; O, 15.00%.
5.3. Preparation of benzofuran-2-carbohydrazides 7
The mixture of hydrazine hydrazide (15 ml) and ethyl benzo-
furan-2-carboxylate (0.01 mole) was stirred at 0e5 ꢀC for 30 min.
The reaction is being monitored by TLC (hexane:ethyl acetate 4:6).
Further, the reaction mixture was stirred at room temperature to
give benzofuran-2-carbohydrazide as a white colored shining
product. mp: 190e194 ꢀC.
5.4.5. (Benzofuran-2-yl)(5-(4-fluorophenyl)-4,5-dihydro-3-
phenylpyrazol-1-yl)methanone (8e)
mp e 220e224, IR (KBr, cmꢂ1): 3055, 2922, 1694, 1646, 1540,
1188, 1114, 966, 1018; 1H NMR (400 MHz)
d (ppm): 3.28 (1H, m),
3.86 (1H, m), 5.80 (1H, m), 7.19 (2H, d, J ¼ 8.0 Hz), 7.28 (2H, d,
J ¼ 8.0 Hz), 7.36 (1H, t), 7.39 (1H, t), 7.50 (3H, m), 7.55 (1H, d,
J ¼ 8.0 Hz), 7.72 (1H, d, J ¼ 8.0 Hz), 7.89 (2H, m), 8.12 (1H, s); 13C
5.4. General procedure of synthesis of benzofuran-2-yl (4,5-
dihydro-3,5-substituted diphenylpyrazol-1-yl) methanones 8aex
NMR (CDCl3) d: 39.9, 59.6, 109.0, 111.6, 115.3, 115.5, 121.0, 123.3,
To a solution of benzofuran hydrazide (0.01 mole) and glacial
acetic acid (10 ml), were added substituted chalcones (0.01 mole).
The reaction mixture was heated in microwave synthesizer for
appropriate time (Table 1). The reaction is being monitored by TLC
using hexane:ethyl acetate (4:6). Aftercompletion of the reaction, the
mixture was poured into crushed ice. Filtered out the separated solid
product and dried under reduced pressure. Finally, it was purified by
flash chromatography using hexaneeethyl acetate as eluents.
124.7, 128.4, 128.6, 128.7, 128.9, 129.2, 129.6, 130.5, 131.1, 134.0,
139.1, 150.0, 151.8, 158.4, 160.9, 165.0; MS m/z ¼ 384 (Mþ), 386
(Mþ2); Anal. Calcd. for C24H17FN2O2: C, 74.99; H, 4.46; N, 7.29; O,
8.32. Found: C, 74.96; H, 4.42; N, 7.22; O, 8.31%.
5.4.6. (Benzofuran-2-yl)(5-(4-chlorophenyl)-4,5-dihydro-3-
phenylpyrazol-1-yl)methanone (8f)
mp e 240e242, IR (KBr, cmꢂ1): 3062, 2926, 1688, 1641, 1547,
1182, 1104, 966, 743; 1H NMR (400 MHz)
d (ppm): 3.21 (1H, m), 3.81
5.4.1. (Benzofuran-2-yl)(4,5-dihydro-3,5-diphenylpyrazol-1-yl)
methanone (8a)
(1H, m), 5.88 (1H, m), 7.13 (2H, d, J ¼ 8.0 Hz), 7.26 (2H, d, J ¼ 8.0 Hz),
7.33 (1H, t), 7.35 (1H, t), 7.56 (3H, m), 7.58 (1H, d, J ¼ 8.0 Hz), 7.82
mp e 210e212, IR (KBr, cmꢂ1): 3059, 2920, 1691, 1641, 1545,
(1H, d, J ¼ 8.0 Hz), 7.88 (2H, m), 8.11 (1H, s); 13C NMR (CDCl3)
d:
1186, 1109, 962; 1H NMR (400 MHz)
d
(ppm): 3.25 (1H, m), 3.88 (1H,
m), 5.84 (1H, m), 7.31 (6H, m), 7.43 (1H, m), 7.49 (3H, m), 7.59 (1H,
m), 7.84 (3H, m), 8.12 (1H, s); 13C NMR (CDCl3)
: 20.8, 40.0, 40.6,
39.9, 59.6, 109.0, 111.6, 121.0, 123.3, 124.7, 128.4, 128.5, 128.6, 128.7,
128.8, 128.9, 129.2, 129.4, 130.5, 131.1, 132.3, 134.0, 141.6, 150.0,
151.8, 158.4, 165.0; MS m/z ¼ 401 (Mþ), 403 (Mþ2); Anal. Calcd. for
C24H17ClN2O2: C, 71.91; H, 4.27; N, 6.99; O, 7.98. Found: C, 71.88; H,
4.24; N, 6.92; O, 7.91%.
d
41.4, 61.3, 111.0, 111.3, 112.0, 115.0, 122.8, 123.1, 123.8, 125.6, 127.1,
127.2, 127.8, 128.9, 130.8, 130.9, 141.3, 146.9, 154.7, 156.1, 156.4; MS
m/z ¼ 366 (Mþ); Anal. Calcd. for C24H18N2O2: C, 78.67; H, 4.95; N,
7.65; O, 8.73. Found: C, 78.64; H, 4.92; N, 7.61; O, 8.70%.
5.4.7. (Benzofuran-2-yl)(5-(2-chlorophenyl)-4,5-dihydro-3-
phenylpyrazol-1-yl)methanone (8g)
5.4.2. (Benzofuran-2-yl)(4,5-dihydro-3-phenyl-5-p-tolylpyrazol-1-
yl)methanone (8b)
mp e 178e182, IR (KBr, cmꢂ1): 3044, 2930, 1694, 1643, 1548,
1183, 1110, 961, 745; 1H NMR (400 MHz)
d
(ppm): 3.25 (1H, m), 3.88
(1H, m), 5.84 (1H, m), 7.09 (3H, m), 7.22 (3H, m), 7.30 (3H, m), 7.42
(1H, m), 7.49 (1H, m), 7.60 (2H, m), 8.02 (1H, s); 13C NMR (CDCl3)
mp e 180e182, IR (KBr, cmꢂ1): 3059, 2941, 1695, 1637, 1546,
1184, 1109, 960; 1H NMR (400 MHz)
d
(ppm): 2.28 (3H, s), 3.26 (1H,
d:
m), 3.82 (1H, m), 5.83 (1H, m), 7.12 (2H, d, J ¼ 8.0 Hz), 7.21 (2H, d,
J ¼ 8.0 Hz), 7.30 (1H, t), 7.42 (1H, t), 7.51 (3H, m), 7.59 (1H, d,
J ¼ 8.0 Hz), 7.76 (1H, d, J ¼ 8.0 Hz), 7.84 (2H, m), 8.03 (1H, s); 13C
39.4, 50.5, 109.0, 111.6, 121.0, 123.3, 124.7, 126.7, 128.2, 128.4, 128.7,
128.8, 128.9, 129.1, 129.2, 130.5, 131.1, 132.3, 134.0, 143.5, 150.0,
151.8, 158.4, 165.0; MS m/z ¼ 401 (Mþ), 403 (Mþ2); Anal. Calcd. for
C24H17ClN2O2: C, 71.91; H, 4.27; N, 6.99; O, 7.98. Found: C, 71.90; H,
4.22; N, 6.92; O, 7.96%.
NMR (CDCl3) d: 21.1, 41.3, 61.1, 112.3, 114.8, 122.8, 123.3, 125.7, 126.9,
127.6, 128.9, 129.6, 130.7, 131.2, 137.5, 138.3, 147.1, 154.9, 156.1, 156.3;
MS m/z ¼ 380 (Mþ); Anal. Calcd. for C25H20N2O2: C, 78.93; H, 5.30;
N, 7.36; O, 8.41. Found: C, 78.91; H, 5.26; N, 7.30; O, 8.40%.
5.4.8. (Benzofuran-2-yl)(4,5-dihydro-5-(4-methoxyphenyl)-3-
phenylpyrazol-1-yl)methanone (8h)
5.4.3. (Benzofuran-2-yl)(4,5-dihydro-5-(4-nitrophenyl)-3-
phenylpyrazol-1-yl)methanone (8c)
mp e 168e170, IR (KBr, cmꢂ1): 3052, 2928, 1692, 1648, 1539,
1184, 1112, 961; 1H NMR (400 MHz)
d (ppm): 2.26 (3H, s), 3.22 (1H,
mp e 170e172, IR (KBr, cmꢂ1): 3032, 2935, 1697, 1600, 1518,
m), 3.81 (1H, m), 5.85 (1H, m), 7.15 (2H, d, J ¼ 8.0 Hz), 7.23 (2H, d,
J ¼ 8.0 Hz), 7.35 (1H, t), 7.42 (1H, t), 7.52 (3H, m), 7.56 (1H, d,
J ¼ 8.0 Hz), 7.76 (1H, d, J ¼ 8.0 Hz), 7.86 (2H, m), 8.06 (1H, s); 13C
1184,1109, 964; 1H NMR (400 MHz)
d
(ppm): 3.29 (1H, m), 3.80 (1H,
m), 5.86 (1H, m), 7.16 (2H, d, J ¼ 8.0 Hz), 7.28 (2H, d, J ¼ 8.0 Hz), 7.41

1946
S. Parekh et al. / European Journal of Medicinal Chemistry 46 (2011) 1942e1948
NMR (CDCl3)
d
: 39.9, 55.9, 59.6, 109.0, 111.6, 114.1, 114.3, 121.0, 123.3,
121.0, 123.3, 124.7, 126.7, 128.2, 128.4, 128.7, 129.0, 129.5, 130.4,
130.6, 130.7, 132.1, 132.3, 136.6, 143.5, 150.0, 151.8, 158.4, 165.0; MS
m/z ¼ 435 (Mþ), 437 (Mþ2); Anal. Calcd. for C24H16Cl2N2O2: C,
66.22; H, 3.70; N, 6.44; O, 7.35. Found: C, 66.20; H, 3.71; N, 6.43; O,
7.30%.
124.7, 128.0, 128.3, 128.4, 128.9, 129.2, 129.6, 130.5, 131.1, 134.0,
135.8, 150.0, 151.8, 158.4, 158.7, 165.0; MS m/z ¼ 396 (Mþ); Anal.
Calcd. for C25H20N2O3: C, 75.74; H, 5.08; N, 7.07; O, 12.11. Found: C,
75.71; H, 5.02; N, 7.01; O, 12.10%.
5.4.9. (Benzofuran-2-yl)(3-(4-chlorophenyl)-4,5-dihydro-5-
phenylpyrazol-1-yl)methanone (8i)
5.4.14. (Benzofuran-2-yl)(3-(4-chlorophenyl)-4,5-dihydro-5-(3,4-
dimethoxyphenyl)pyrazol-1-yl)methanone (8n)
mp e 154e156, IR (KBr, cmꢂ1): 3064, 2962, 1695, 1641, 1548,
mp e 188e190, IR (KBr, cmꢂ1): 3063, 2928, 1694, 1638, 1541,
1186, 1114, 964, 756; 1H NMR (400 MHz)
d
(ppm): 3.21 (1H, m), 3.96
1182, 1109, 958, 742; 1H NMR (400 MHz)
d (ppm): 3.21 (1H, m), 3.92
(1H, m), 5.84 (1H, m), 7.29 (3H, m), 7.35 (3H, m), 7.46 (1H, m), 7.52
(1H, m), 3.98 (6H, s), 5.84 (1H, m), 6.61 (3H,m), 7.19 (2H, m), 7.42
(2H, d, J ¼ 8 Hz), 7.60 (1H, d, J ¼ 8 Hz), 7.86 (1H, d, J ¼ 8 Hz), 7.90
(1H, d, J ¼ 8.0 Hz), 7.49 (1H, d, J ¼ 8.0 Hz), 7.54 (2H, d, J ¼ 8.0 Hz),
(2H, d, J ¼ 8 Hz), 8.08 (1H, s); 13C NMR (CDCl3)
d: 39.9, 59.6, 109.0,
7.94 (2H, d, J ¼ 8 Hz), 8.06 (1H, s); 13C NMR (CDCl3)
d: 39.9, 56.2,
111.6, 121.0, 123.3, 124.7, 126.8, 127.0, 127.5, 128.3, 128.6, 129.0,
129.4, 130.5, 130.6, 130.8, 132.1, 136.6, 143.5, 150.0, 151.8, 158.4,
165.0; MS m/z ¼ 401 (Mþ), 403 (Mþ2); Anal. Calcd. for
C24H17ClN2O2: C, 71.91; H, 4.27; N, 6.99; O, 7.98. Found: C, 71.87; H,
4.24; N, 6.96; O, 7.97%.
56.5, 59.9, 109.0, 111.6, 112.0, 115.1, 120.3, 121.0, 123.3, 124.7, 129.0,
129.1, 130.5, 130.6, 130.7, 132.1, 136.6, 136.8, 147.8, 149.6, 150.0, 151.8,
158.4, 165.0; MS m/z ¼ 461 (Mþ), 463 (Mþ2); Anal. Calcd. for
C26H21ClN2O4: C, 67.75; H, 4.59; N, 6.08; O,13.89. Found: C, 67.71; H,
4.55; N, 6.09; O, 13.80%.
5.4.10. (3,5-bis(4-chlorophenyl)-4,5-dihydropyrazol-1-yl)
(Benzofuran-2-yl)methanone (8j)
5.4.15. (Benzofuran-2-yl)(3-(4-chlorophenyl)-4,5-dihydro-5-p-
tolylpyrazol-1-yl)methanone (8o)
mp e 176e178, IR (KBr, cmꢂ1): 3061, 2924, 1691, 1643, 1550,
mp e 178e182, IR (KBr, cmꢂ1): 3061, 2925, 1696, 1648, 1541,
1180, 1116, 963, 744; 1H NMR (400 MHz)
d
(ppm): 3.21 (1H, m), 3.96
1180, 1111, 967, 750; 1H NMR (400 MHz)
d (ppm): 2.29 (3H, s), 3.28
(1H, m), 5.84 (1H, m), 7.06 (2H, d, J ¼ 8 Hz), 7.19 (2H, m), 7.22 (2H, d,
(1H, m), 3.96 (1H, m), 5.86 (1H, m), 7.11 (2H, d, J ¼ 8 Hz), 7.16 (2H,
m), 7.27 (2H, d, J ¼ 8 Hz), 7.30 (2H, d, J ¼ 8 Hz), 7.47 (1H, d, J ¼ 8 Hz),
7.50 (1H, d, J ¼ 8 Hz), 7.66 (2H, d, J ¼ 8 Hz), 8.12 (1H, s); 13C NMR
J ¼ 8 Hz), 7.30 (2H, d, J ¼ 8 Hz), 7.42 (1H, d, J ¼ 8 Hz), 7.49 (1H, d,
J ¼ 8 Hz), 7.60 (2H, d, J ¼ 8 Hz), 8.08 (1H, s); 13C NMR (CDCl3)
d: 39.9,
59.6, 109.0, 111.6, 121.0, 123.3, 124.7, 128.4, 128.5, 128.7, 128.9, 129.0,
129.7, 130.1, 130.4, 130.6, 132.1, 132.3, 136.6, 141.6, 150.0, 151.8, 158.4,
165.0; MS m/z ¼ 435 (Mþ), 437 (Mþ2); Anal. Calcd. for
C24H16Cl2N2O2: C, 66.22; H, 3.70; N, 6.44; O, 7.35. Found: C, 66.21;
H, 3.66; N, 6.44; O, 7.31%.
(CDCl3) d: 23.3, 24.3, 39.9, 59.6, 109.0, 111.6, 121.0, 124.7, 126.3,
126.9, 128.5, 128.9, 129.0, 129.4, 130.5, 130.6, 130.8, 132.1, 136.4,
136.6, 140.5, 150.0, 151.8, 158.4, 165.0; MS m/z ¼ 415 (Mþ), 417
(Mþ2); Anal. Calcd. for C25H19ClN2O2: C, 72.37; H, 4.62; N, 6.75; O,
7.71. Found: C, 72.32; H, 4.60; N, 6.70; O, 7.70%.
5.4.11. (Benzofuran-2-yl)(3-(4-chlorophenyl)-4,5-dihydro-5-(4-
methoxyphenyl)pyrazol-1-yl)methanone (8k)
5.4.16. (Benzofuran-2-yl)(3-(4-chlorophenyl)-5-(4-fluorophenyl)-
4,5-dihydropyrazol-1-yl)methanone (8p)
mp e 188e190, IR (KBr, cmꢂ1): 3052, 2921, 1691, 1646, 1547,
mp e 220e222, IR (KBr, cmꢂ1): 3048, 2927, 1695, 1650, 1541,
1181, 1109, 968, 748; 1H NMR (400 MHz)
d
(ppm): 2.26 (3H, s), 3.24
1190, 1115, 968, 746, 1020; 1H NMR (400 MHz)
d (ppm): 3.24 (1H,
(1H, m), 3.98 (1H, m), 5.81 (1H, m), 7.01 (2H, d, J ¼ 8 Hz), 7.14 (2H,
m), 7.23 (2H, d, J ¼ 8 Hz), 7.32 (2H, d, J ¼ 8 Hz), 7.44 (1H, d, J ¼ 8 Hz),
7.48 (1H, d, J ¼ 8 Hz), 7.62 (2H, d, J ¼ 8 Hz), 8.06 (1H, s); 13C NMR
m), 3.92 (1H, m), 5.81 (1H, m), 7.08 (2H, d, J ¼ 8 Hz), 7.17 (2H, m),
7.26 (2H, d, J ¼ 8 Hz), 7.34 (2H, d, J ¼ 8 Hz), 7.40 (1H, d, J ¼ 8 Hz), 7.48
(1H, d, J ¼ 8 Hz), 7.64 (2H, d, J ¼ 8 Hz), 8.04 (1H, s); 13C NMR (CDCl3)
(CDCl3)
d
: 39.9, 55.9, 59.6, 109.0, 111.6, 114.1, 114.4, 121.0, 123.3,
d: 39.9, 59.6, 109.0, 111.6, 115.3, 115.6, 121.0, 123.3, 124.7, 128.6,
124.7, 128.0, 128.6, 129.0, 129.4, 130.5, 130.6, 130.7, 132.1, 135.8,
136.6, 150.0, 151.8, 158.4, 158.7, 165.0; MS m/z ¼ 431 (Mþ), 433
(Mþ2); Anal. Calcd. for C25H19ClN2O3: C, 69.69; H, 4.44; N, 6.50; O,
11.14. Found: C, 69.65; H, 4.46; N, 6.44; O, 11.12%.
128.8, 129.0, 129.3, 130.5, 130.6, 130.8, 132.1, 136.6, 139.1, 150.0,
151.8, 158.4, 160.9, 165.0; MS m/z ¼ 419 (Mþ), 421 (Mþ2); Anal.
Calcd. for C24H16ClFN2O2: C, 68.82; H, 3.85; N, 6.69; O, 7.64. Found:
C, 68.80; H, 3.81; N, 6.62; O, 7.61%.
5.4.12. (Benzofuran-2-yl)(3-(4-chlorophenyl)-4,5-dihydro-5-(4-
nitrophenyl)pyrazol-1-yl)methanone (8l)
5.4.17. (Benzofuran-2-yl)(3-(4-fluorophenyl)-4,5-dihydro-5-
phenylpyrazol-1-yl)methanone (8q)
mp e 192e194, IR (KBr, cmꢂ1): 3050, 2930, 1688, 1640, 1546,
mp e 244e246, IR (KBr, cmꢂ1): 3051, 2927, 1694, 1648, 1536,
1181, 1115, 963, 745; 1H NMR (400 MHz)
d
(ppm): 3.25 (1H, m), 3.94
1186, 1109, 955, 1018; 1H NMR (400 MHz)
d (ppm): 3.20 (1H, m),
(1H, m), 5.81 (1H, m), 7.02 (2H, d, J ¼ 8 Hz), 7.14 (2H, m), 7.26 (2H, d,
3.87 (1H, m), 5.80 (1H, m), 7.27 (8H, m), 7.38 (1H, t), 7.50 (1H, d),
J ¼ 8 Hz), 7.34 (2H, d, J ¼ 8 Hz), 7.41 (1H, d, J ¼ 8 Hz), 7.45 (1H, d,
7.75 (1H, d, J ¼ 8), 7.84 (2H, q), 7.97 (1H, s); 13C NMR (CDCl3)
d: 39.9,
J ¼ 8 Hz), 7.61 (2H, d, J ¼ 8 Hz), 8.12 (1H, s); 13C NMR (CDCl3)
d: 39.9,
59.6, 109.0, 111.6, 115.6, 115.7, 121.0, 123.3, 124.7, 126.8, 127.0, 127.4,
128.2, 128.6, 129.6, 130.5, 130.7, 130.8, 143.5, 150.0, 151.8, 158.4,
165.0, 165.2; MS m/z ¼ 384 (Mþ), 386 (Mþ2); Anal. Calcd. for
C24H17FN2O2: C, 74.99; H, 4.46; N, 7.29; O, 8.32. Found: C, 74.96; H,
4.40; N, 7.25; O, 8.30%.
59.6, 109.0, 111.6, 120.5, 120.9, 121.0, 123.3, 124.7, 127.3, 127.9, 129.0,
129.2, 130.5, 130.6, 130.8, 132.1, 136.6, 146.4, 149.6, 150.0, 151.8,
158.4, 165.0; MS m/z ¼ 446 (Mþ), 448 (Mþ2); Anal. Calcd. for
C24H16ClN3O4: C, 64.65; H, 3.62; N, 9.42; O, 14.35. Found: C, 64.62;
H, 3.60; N, 9.40; O, 14.31%.
5.4.18. (Benzofuran-2-yl)(5-(4-chlorophenyl)-3-(4-fluorophenyl)-
4,5-dihydropyrazol-1-yl)methanone (8r)
5.4.13. (Benzofuran-2-yl)(5-(2-chlorophenyl)-3-(4-chlorophenyl)-
4,5-dihydropyrazol-1-yl)methanone (8m)
mp e 210e212, IR (KBr, cmꢂ1): 3036, 2922, 1686, 1643, 1548,
mp e 160e162, IR (KBr, cmꢂ1): 3064, 2926, 1696, 1641, 1540,
1182, 1112, 954, 740, 1020; 1H NMR (400 MHz)
d (ppm): 3.26 (1H,
1186, 1109, 957, 748; 1H NMR (400 MHz)
d
(ppm): 3.21 (1H, m), 3.96
m), 3.96 (1H, m), 5.85 (1H, m), 7.35 (7H, m), 7.46 (1H, m), 7.57 (1H,
(1H, m), 5.84 (1H, m), 7.09 (3H, m), 7.22 (3H, m), 7.42 (1H, d,
d, J ¼ 8 Hz), 7.82 (1H, m), 7.92 (2H, m), 8.04 (1H, s); 13C NMR (CDCl3)
J ¼ 8 Hz), 7.49 (1H, d, J ¼ 8 Hz), 7.52 (2H, d, J ¼ 8 Hz), 7.90 (2H, d,
d: 39.9, 59.6, 109.0, 111.6, 115.4, 115.6, 121.0, 123.3, 124.7, 128.4,
J ¼ 8 Hz), 8.12 (1H, s); 13C NMR (CDCl3)
d
: 39.4, 50.5, 109.0, 111.6,
128.5, 128.7, 128.8, 129.6, 130.3, 130.5, 130.8, 132.3, 141.6, 150.0,

S. Parekh et al. / European Journal of Medicinal Chemistry 46 (2011) 1942e1948
1947
151.8,158.4,165.0,165.2; MS m/z ¼ 419 (Mþ), 421(Mþ2); Anal. Calcd.
for C24H16ClFN2O2: C, 68.82; H, 3.85; N, 6.69; O, 7.64. Found: C,
68.80; H, 3.81; N, 6.65; O, 7.60%.
140.5, 150.0, 151.8, 158.4, 165.0, 165.2; MS m/z ¼ 398 (Mþ), 400
(Mþ2); Anal. Calcd. for C25H19FN2O2: C, 75.36; H, 4.81; N, 7.03; O,
8.03. Found: C, 75.30; H, 4.81; N, 7.00; O, 8.01%.
5.4.19. (Benzofuran-2-yl)(3-(4-fluorophenyl)-4,5-dihydro-5-(4-
methoxyphenyl)pyrazol-1-yl)methanone (8s)
5.4.24. (3,5-bis(4-fluorophenyl)-4,5-dihydropyrazol-1-yl)
(Benzofuran-2-yl)methanone (8x)
mp e 220e222, IR (KBr, cmꢂ1): 3050, 2918, 1696, 1644, 1546,
mp e 184e186, IR (KBr, cmꢂ1): 3042, 2935, 1696, 1656, 1542,
1196, 1115, 964, 1020; 1H NMR (400 MHz)
d
(ppm): 2.22 (3H, s), 3.29
1180, 1115, 966, 1022; 1H NMR (400 MHz)
d (ppm): 3.20 (1H, m),
(1H, m), 3.93 (1H, m), 5.87 (1H, m), 7.06 (2H, d, J ¼ 8 Hz), 7.15 (2H,
m), 7.29 (2H, d, J ¼ 8 Hz), 7.36 (2H, d, J ¼ 8 Hz), 7.47 (1H, d, J ¼ 8 Hz),
7.43 (1H, d, J ¼ 8 Hz), 7.66 (2H, d, J ¼ 8 Hz), 8.12 (1H, s); 13C NMR
3.94 (1H, m), 5.87 (1H, m), 7.00 (2H, d, J ¼ 8 Hz), 7.14 (2H, m), 7.28
(2H, d, J ¼ 8 Hz), 7.38 (2H, d, J ¼ 8 Hz), 7.46 (1H, d, J ¼ 8 Hz), 7.49
(1H, d, J ¼ 8 Hz), 7.67 (2H, d, J ¼ 8 Hz), 8.05 (1H, s); 13C NMR (CDCl3)
(CDCl3)
d
: 39.9, 55.9, 59.6,109.0,111.6,114.1,114.5,115.6,115.8,121.0,
d: 39.9, 59.6, 109.0, 111.6, 115.3, 115.6, 115.8, 115.9, 121.0, 123.3, 124.7,
123.3, 124.7, 128.0, 128.6, 129.6, 130.5, 130.6, 130.8, 135.8, 150.0,
151.8,158.4, 158.7,165.0, 165.2; MS m/z ¼ 414 (Mþ), 416 (Mþ2); Anal.
Calcd. for C25H19FN2O3: C, 72.45; H, 4.62; N, 6.76; O, 11.58. Found: C,
72.42; H, 4.60; N, 6.70; O, 11.51%.
128.3, 128.6, 129.6, 130.5, 130.8, 130.9, 139.1, 150.0, 151.8, 158.4,
160.9, 165.0, 165.2; MS m/z ¼ 402 (Mþ), 404 (Mþ2); Anal. Calcd. for
C24H16F2N2O2: C, 71.64; H, 4.01; N, 6.96; O, 7.95. Found: C, 71.60; H,
4.01; N, 6.92; O, 7.90%.
5.4.20. (Benzofuran-2-yl)(3-(4-fluorophenyl)-4,5-dihydro-5-(4-
nitrophenyl)pyrazol-1-yl)methanone (8t)
6. Conclusion
mp e 240e244, IR (KBr, cmꢂ1): 3063, 2921, 1694, 1641, 1547,
We have demonstrated a facile and rapid synthesis of benzo-
furan-2-yl(4,5-diydro-3,5-substituted diphenylpyrazol-1-yl) meth-
anonesundermicrowave irradiation. Allthesynthesized compounds
were examined for antiproliferative activityand the ability to reverse
multidrug resistance in human MDR1-gene transfected mouse
lymphoma (MDR) cells in vitro. In our experiments the anti-
proliferative effects, the IC50 values of the compounds were similar,
concentration however the inhibitory action on the function of over
expressed ABC transporter in cancer cells were strictly dependent on
the chemical structures of benzofuran methanones, resulting in
increased rhodamine accumulation in cancer cell model. The
compounds 8b, 8c, 8f, 8h and 8k were found high inhibitory effect
against MDR reversal activity.
1190, 1114, 964, 1028; 1H NMR (400 MHz)
d (ppm): 3.28 (1H, m),
3.91 (1H, m), 5.87 (1H, m), 7.05 (2H, d, J ¼ 8 Hz), 7.18 (2H, m), 7.20
(2H, d, J ¼ 8 Hz), 7.31 (2H, d, J ¼ 8 Hz), 7.47 (1H, d, J ¼ 8 Hz), 7.48 (1H,
d, J ¼ 8 Hz), 7.64 (2H, d, J ¼ 8 Hz), 8.02 (1H, s); 13C NMR (CDCl3)
d:
39.9, 59.6, 109.0, 111.6, 115.5, 115.6, 120.3, 120.9, 121.0, 123.3, 124.7,
127.5, 127.9, 129.6, 130.2, 130.5, 130.8, 146.4, 149.6, 150.0, 151.8,
158.4, 165.0, 165.2; MS m/z ¼ 429 (Mþ), 431 (Mþ2); Anal. Calcd. for
C24H16FN3O4: C, 67.13; H, 3.76; N, 9.79; O, 14.90. Found: C, 67.10; H,
3.71; N, 9.77; O, 14.88%.
5.4.21. (Benzofuran-2-yl)(5-(2-chlorophenyl)-3-(4-fluorophenyl)-
4,5-dihydropyrazol-1-yl)methanone (8u)
mp e 176e178, IR (KBr, cmꢂ1): 3048, 2926, 1697, 1641, 1541,
1188, 1112, 960, 744, 1022; 1H NMR (400 MHz)
d (ppm): 3.20 (1H,
Acknowledgment
m), 3.93 (1H, m), 5.82 (1H, m), 7.02 (3H, m), 7.26 (3H, m), 7.41 (1H,
d, J ¼ 8 Hz), 7.45 (1H, d, J ¼ 8 Hz), 7.57 (2H, d, J ¼ 8 Hz), 7.94 (2H, d,
J ¼ 8 Hz), 8.06 (1H, s); 13C NMR (CDCl3)
d: 39.4, 50.5, 109.0, 111.6,
The authors are thankful to FIST-DST and SAP-UGC for their
generous financial and instrumentation support. Special thanks are
due to “National Facility for Drug Discovery through NCE’s Devel-
115.4, 115.6, 121.0, 123.3, 124.7, 126.7, 128.2, 128.4, 128.7, 129.6,
130.5, 130.7, 130.8, 132.3, 143.5, 150.0, 151.8, 158.4, 165.0, 165.2; MS
m/z ¼ 419 (Mþ), 421 (Mþ2); Anal. Calcd. for C24H16ClFN2O2: C,
68.82; H, 3.85; N, 6.69; O, 7.64. Found: C, 68.80; H, 3.81; N, 6.66; O,
7.61%.
opment
& Instrumentation Support to Small Manufacturing
Pharma Enterprises” Programme under DPRS jointly funded by DST
New Delhi, Government of Gujarat Industries Commissionerate &
Saurashtra University Rajkot. We are also thankful to SAIF, CIL,
Chandigarh for providing spectroscopic analysis. The authors
express their sincere gratitude to Anikó Váradi Vigyikánné for her
technical assistance from the Department of Medical Microbiology
and Immunobiology (University of Szeged, Hungary) and for the
financial support to the Szeged Foundation for Cancer Research
(Hungary).
5.4.22. (Benzofuran-2-yl)(3-(4-fluorophenyl)-4,5-dihydro-5-(3,4-
dimethoxyphenyl)pyrazol-1-yl)methanone (8v)
mp e 164e166, IR (KBr, cmꢂ1): 3038, 2938, 1690, 1655, 1544,
1184, 1112, 960, 1021; 1H NMR (400 MHz)
d (ppm): 3.29 (1H, m),
3.96 (1H, m), 3.88 (6H, s), 5.89 (1H, m), 6.70 (3H,m), 7.29 (2H, m),
7.48 (1H, d, J ¼ 8.0 Hz), 7.55 (1H, d, J ¼ 8.0 Hz), 7.59 (2H, d,
J ¼ 8.0 Hz), 7.90 (2H, d, J ¼ 8 Hz), 8.08 (1H, s); 13C NMR (CDCl3)
d:
39.9, 56.2, 56.5, 59.9, 109.0, 111.6, 112.0, 115.1, 115.6, 115.7, 120.3,
121.0, 123.3, 124.7, 129.6, 130.5, 130.6, 130.8, 136.8, 147.8, 149.6,
150.0, 151.8, 158.4, 165.0, 165.2; MS m/z ¼ 444 (Mþ), 446 (Mþ2);
Anal. Calcd. for C26H21FN2O4: C, 70.26; H, 4.76; N, 6.30; O, 14.40.
Found: C, 70.22; H, 4.70; N, 6.31; O, 14.38%.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ejmech.2011.02.045.
References
5.4.23. (Benzofuran-2-yl)(3-(4-fluorophenyl)-4,5-dihydro-5-p-
tolylpyrazol-1-yl)methanone (8w)
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