Synthesis, Characterization, and Comparative Study of Some Heterocyclic Compounds Containing Isoniazid and Nicotinic Acid Hydrazide Moieties

Article abstract of DOI:10.1134/S1070428020100218

Abstract: Some new derivatives of six-membered heterocyclic compounds containingisoniazid and nicotinic acid hydrazide fragments have been synthesized accordingto green procedures with excellent yields. The structures of the synthesizedcompounds were conf

Full text of DOI:10.1134/S1070428020100218

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 10, pp. 1795–1800. © Pleiades Publishing, Ltd., 2020.
Synthesis, Characterization, and Comparative Study
of Some Heterocyclic Compounds Containing Isoniazid
and Nicotinic Acid Hydrazide Moieties
M. Zalaa,*, J. J. Voraa, and H. B. Patelb
a Department of Chemistry, M. G. Science Institute, Gujarat University,
Ahmedabad, Gujarat, 380009 India
b Department of Chemistry, LJ Institute of Applied Sciences, Gujarat University,
Ahmedabad, Gujarat, 380009 India
*e-mail: zalamayursinh2794@gmail.com
Received May 25, 2020; revised June 10, 2020; accepted June 16, 2020
Abstract—Some new derivatives of six-membered heterocyclic compounds containing isoniazid and nicotinic
acid hydrazide fragments have been synthesized according to green procedures with excellent yields. The
1
structures of the synthesized compounds were confirmed by H and 13C NMR, IR, and mass spectra and
elemental analyses. The compounds were screened for their in vitro antibacterial and antifungal activities. The
results showed that the isoniazid derivatives are more active than their analogs containng a nicotinic hydrazide
moiety.
Keywords: isoniazid, nicotinic hydrazide, antimicrobial activity
DOI: 10.1134/S1070428020100218
INTRODUCTION
meric to isoniazid has multiple applications and has
long been known as biologically active compound.
Pyridine derivatives have remarkable pharmaceutical
importance because of their biological activity as anti-
HIV [6], antitubercular, antimicrobial [7], antidiabetic
[8], anti-inflammatory [9], antiplasmodial [10], and
anticancer [11] activities. Our goal was to synthesize
and evaluate biological activity of some isoniazid and
nicotinic acid hydrazide derivatives.
Investigation of heterocyclic compounds is an inter-
esting topic from both theoretical and practical points
of view. There are a huge number of pharmacologically
active heterocyclic compounds, many of which are in
regular clinical use. Nitrogen heterocycles are most
copious in nature than those containing oxygen or
sulfur. Heterocyclic compounds are crucial to life in
different ways. Most of sugars and their derivatives,
including vitamins and some members of vitamin B
group, have heterorings with a nitrogen atom. Analysis
of the US FDA-approved drugs database shows that
59% of small-molecule drugs contain nitrogen hetero-
atom in a heterocycle [1]. Nitrogen-containing six-
membered heterocyclic compounds have acquired
enormous significance in the field of drug discovery. In
this work we report the synthesis and comparative
study of antimicrobial activities of two types of six-
membered heterocyclic compounds derived from
isoniazid and nicotinic acid hydrazide. Isoniazid is
isonicotinic acid hydrazide which plays a vital role in
the manufacture of various drugs such as anticancer,
antitubercular, antifungal, antibacterial, and antiviral
agents [2–5]. Nicotinic acid hydrazide which is iso-
RESULTS AND DISCUSSION
In this study, new series of bipyrazole derivatives
bearing isoniazid and nicotinic acid hydrazide moieties
were synthesized as shown in Scheme 1. The starting
compounds, 1H-pyrazole-4-carbaldehydes 4a and 4b
were prepared by the Vilsmeier–Haack reaction accord-
ing to literature procedure [12]. The key intermediates,
chalcones 6a–6d were synthesized in good to excellent
yields by base-catalyzed Claisen–Schmidt condensa-
tion of aldehydes 4a and 4b with 2-acetylthiophene
(5a) and 2-acetylfuran (5b) in the presence of NaOH
(5 mol %) in aqueous ethanol at room temperature.
Finally, cyclization of 6a–6d with isoniazid and nico-
tinic acid hydrazide using NaOH as catalyst in ethanol
1795

ZALA et al.
1796
Scheme 1.
Ph
H
N
N
O
N
Ph
N
AcOH/EtOH
reflux
DMF/POCl3
90°C, 4 h
NHNH2
Me
Me
+
CHO
R
R
R
1
2a, 2b
3a, 3b
4a, 4b
O
Ph
N
NHNH2
R
N
N
7a
NaOH/EtOH
r.t., 8–9 min
O
O
N
X
N
Ph
Me
5a, 5b
X
N
N
NaOH/EtOH
r.t., 1–2 h
N
8a–8d
O
R
Ph
N
N
NHNH2
X
R
N
7b
O
NaOH/EtOH
r.t., 8–9 min
6a–6d
O
N
X
N
N
9a–9d
R = H (a, b), MeO (c, d); X = S (a, c), O (b, d).
at room temperature afforded target compounds 8a–8d
and 9a–9d, respectively (Scheme 1).
medium for the test bacteria, and Sabouraud dextrose
broth was used for fungi. The inoculum size for the test
strains was adjusted to 108 CFU per milliliter according
to the McFarland turbidity standards. Each compound
was dissolved in DMSO to a stock concentration of
2000 μg/mL. Primary and secondary screenings were
performed. All compounds were screened for their
antibacterial activity against Bacillus subtilis (MTCC
441), Clostridium tetani (MTCC 449), Staphylococcus
aureus (MTCC 96), Escherichia coli (MTCC 443),
Salmonella typhi (MTCC 98), Candida albicans
(MTCC 227), and Trichophyton rubrum (MTCC 296)
at concentrations of 1000, 500, and 250 μg/mL for
primary screening. Stock solutions were diluted with
DMSO to get the desired concentration. The com-
pounds that showed antimicrobial activity in the pri-
mary screening were further screened at concentrations
of 200, 100, 62.5, 50, and 25 μg/mL. A 10-μL portion
of each solution was inoculated in a 96-well plate, and
microbial growth was noted after 24 and 48 h. The
lowest concentration at which no visible growth
(turbidity) was observed was considered as the mini-
The structure of 8a–8d and 9a–9d was confirmed
1
by elemental analyses and FT-IR, H and 13C NMR,
and mass spectra. In the IR spectra of 8a–8d and 9a–
9d, the C–H stretching band was observed at 2925–
3025 cm–1, and the C=N and C=O stretchings were
observed at 1587–1610 and 1685–1710 cm–1, respec-
tively. In the 1H NMR spectra of these compounds, the
4-H protons of the dihydropyrazole ring resonated as
multiplets at δ 3.29–3.45 and 4.05-4.17 ppm. The 5-H
proton of the same ring appeared as a multiplet at
δ 5.82–5.99 ppm due to vicinal coupling with the two
magnetically nonequivalent protons on C4. The mass
spectra of all compounds 8 and 9 showed the molecular
ion peak in conformity with the assigned structure.
All compounds 8a–8d and 9a–9d were screened for
their antibacterial and antifungal activities using the
broth dilution method recommended by the National
Committee for Clinical Laboratory Standards (NCCLS)
[13, 14]. Mueller–Hinton broth was used as the nutrient
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

SYNTHESIS, CHARACTERIZATION, AND COMPARATIVE STUDY
1797
Table 1. In vitro antimicrobial activity of compounds 8a–8d and 9a–9d (MIC, μg/mL)
Gram-positive bacteria
Gram-negative bacteria
Fungi
Compd. no.
B. subtilis
C. tetani
250
50
S. aureus
E. coli
200
500
200
250
250
200
200
125
100
50
S. typhi
200
500
250
250
250
200
250
100
100
50
V. cholerae C. albicans T. rubrum
8a
8b
8c
8d
9a
9b
9c
9d
250
100
250
200
500
500
250
125
100
50
500
500
125
62.5
250
200
250
500
100
50
250
100
200
200
500
500
250
100
250
50
>1000
500
1000
1000
1000
500
1000
250
–
>1000
500
500
1000
1000
500
>1000
100
–
100
250
250
200
200
500
250
50
Ampicillin
Chloramphenicol
Ciprofloxacin
Norfloxacin
Nystatin
–
–
50
100
50
25
25
25
50
–
–
10
10
10
10
100
–
–
–
–
–
–
–
–
100
500
100
100
Griseofulfin
–
–
–
–
–
–
mum inhibitory concentration (MIC). Ampicillin,
chloramphenicol, ciprofloxacin, and norfloxacin were
used as standard antibacterial drugs, and nystatin and
griseofulvin were used as standard antifungal drugs.
The results are summarized in Table 1.
layer chromatography (TLC) on aluminum plates
coated with silica gel 60 F254 (Merck); layer thickness
0.25 mm. The components were visualized by exposure
to UV light or iodine vapor. The melting points were
measured in open capillary tubes on an Electrothermal
melting point apparatus. The IR spectra were recorded
with a FTIR MB 3000 spectrophotometer using ZnSe
optics (490–8500 cm–1). The mass spectra were
recorded on a Shimadzu LCMS 2010 spectrometer
(Japan). The 1H and 13C NMR spectra were recorded in
DMSO-d6 on a Bruker Avance 400 spectrometer at 400
and 100 MHz, respectively, using the residual proton
and carbon signals of the solvent as internal standard.
The elemental analysis was done with a Perkin Elmer
2400 Series II elemental analyzer (USA).
Isoniazid derivatives 8a–8d showed a good antibac-
terial activity compared to nicotinic acid hydrazide
derivatives 9a–9d. Compound 8b was found to be
equipotent to ampicillin against gram-positive
B. subtilis (MIC 100 μg/mL), and its activity against
C. tetani (MIC 50 μg/mL) was higher than those of
ampicillin (MIC 250 μg/mL) and ciprofloxacin (MIC
100 μg/mL) and was comparable to that of norfloxacin.
The activity of 8c against C. tetani (MIC 100 μg/mL)
was similar to that of ciprofloxacin. Compound 8d was
more active than ampicillin against S. aureus (MIC
62.5 and 100 μg/mL, respectively), whereas its activity
against gram-negative E. coli was comparable to the
activity of ampicillin (MIC 100 μg/mL). The synthe-
sized isoniazid derivatives showed moderate to good
antifungal activity, whereas the nicotinic acid hydrazide
derivatives showed moderate to low antifungal activity.
Thus, isoniazid derivatives 8a–8d proved to be more
effective against all microorganisms than nicotinic
hydrazide derivatives 9a–9d.
General procedure for the synthesis of 1-phenyl-
2-[1-(4-R-phenyl)ethylidene]hydrazines 3a and 3b.
Phenylhydrazine (0.1 mol) and 3-4 drops of acetic acid
were added to a solution of acetophenone or p-me-
thoxyacetophenone (0.1 mol) in anhydrous ethanol
(20 mL), and the mixture was stirred at 70–80°C for
1 h. The mixture was then left to stand at room tem-
perature, and the solid product was filtered off, washed
with ethanol, and dried. Compounds 3a and 3b were
sufficiently pure and were used without further
purification.
EXPERIMENTAL
General procedure for the synthesis of
3-(4-R-phenyl)-1-phenyl-1H-pyrazole-4-carbalde-
hydes 4a and 4b. Cold DMF (0.4 mol) was added
dropwise with stirring over a period of 30 min to
All reagents (analytical grade) were purchased from
Sigma–Aldrich and were used without further purifica-
tion. The progress of reactions was monitored by thin-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

ZALA et al.
1798
phosphoryl chloride (0.4 mol), and the mixture was
stirred for further 45 min at 0°C. Compound 3a or 3b
(0.08 mol) was then added, and the mixture was
allowed to warm up to room temperature, heated at
90°C for 4 h, cooled, and poured into a mixture of
crushed ice and water. The solid product was filtered
off, dried, and recrystallized from chloroform–
methanol (1:1).
δC, ppm: 56.5, 119.2, 119.8, 121.6, 122.5, 123.1, 126.4,
126.7, 127.4, 128.2, 128.6, 129.1, 129.8, 130.4, 131.5,
132.2, 133.8, 134.6, 139.4, 150.0, 150.8, 163.3, 186.4
General procedure for the synthesis of com-
pounds 8a–8d and 9a–9d [15, 16]. A mixture of com-
pound 6a–6d, isoniazid (7a) or nicotinic acid hydrazide
(7b), aqueous sodium hydroxide, and ethanol (10 mL)
was stirred at room temperature for 8–9 min. After
completion of the reaction, the solid product was
filtered off and recrystallized from methanol.
General procedure for the synthesis of
(E)-3-[1-phenyl-3-(4-R-phenyl)-1H-pyrazol-4-yl]-1-
[thiophen(or furan)-2-yl]prop-2-en-1-ones 6a–6d.
Equimolar amounts of compound 4a or 4b and 2-ace-
tylthiophene (5a) or 2-acetylfuran (5b) were added to
a solution of sodium hydroxide (5 mol %) in a water–
ethanol mixture (1:2, 30 mL). The mixture was stirred
at room temperature for 1–2 h, and the solid product
was filtered off, and recrystallized from methanol.
{1′,3′-Diphenyl-5-(thiophen-2-yl)-3,4-dihydro-
1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-4-yl)metha-
none (8a). Yield 86%, mp 226–228°C. IR spectrum, ν,
cm–1: 3017 (C–Harom), 1695 (C=N), 1560 (C=C).
1H NMR spectrum, δ, ppm: 3.36 d.d (1H, 4-H),
4.07 d.d (1H, 4-H), 5.82 d.d (1H, 5-H), 7.10–8.76 m
(18H, Harom). 13C NMR spectrum, δC, ppm: 40.6, 61.5,
117.2, 119.9, 121.7, 123.1, 124.4, 125.8, 126.2, 127.2,
129.2, 129.3, 140.8, 149.7, 155.6, 167.2. Mass spec-
trum (ESI), m/z (Irel, %): 475.15 (100.0), 476.15 (30.3),
477.14 (4.5), 477.15 (2.7), 476.14 (1.8), 477.15 (1.7),
478.15 (1.4). Calculated for C28H21N5OS: M 475.57.
(E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-1-(thio-
phen-2-yl)prop-2-en-1-one (6a). Yield 92%, mp 139–
141°C. IR spectrum, ν, cm–1: 3017 (C–Harom), 1694
(C=O), 1567 (C=C). 1H NMR spectrum, δ, ppm: 7.10–
8.18 m (15H, Harom, CH=CH), 9.35 s (1H, 5-H).
13C NMR spectrum, δC, ppm: 118.5, 119.4, 121.5,
122.2, 122.6, 126.1, 126.6, 127.3, 128.4, 128.6, 128.9,
129.5, 130.4, 131.5, 132.2, 133.5, 134.3, 139.5, 150.1,
150.4, 162.9, 186.4.
{5-(Furan-2-yl)-1′,3′-diphenyl-3,4-dihydro-
1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-4-yl)metha-
none (8b). Yield 88%, mp 235–238°C. IR spectrum, ν,
cm–1: 3017 (C–Harom), 1696 (C=N), 1563 (C=C).
1H NMR spectrum, δ, ppm: 3.44 d.d (1H, 4-H),
4.16 d.d (1H, 4-H), 5.92 d.d (1H, 5-H), 7.04–8.77 m
(18H, Harom). 13C NMR spectrum, δC, ppm: 38.1, 55.8,
59.1, 109.4, 109.9, 114.2, 117.2, 119.9, 121.7, 123.2,
126.2, 128.5, 129.3, 139.7, 140.8, 141.7, 142.1, 149.7,
149.9, 155.6, 160.6, 167.2. Mass spectrum (ESI), m/z
(Irel, %): 459.17 (100.0), 460.17 (30.3), 461.18 (2.7),
460.17 (1.8), 461.18 (1.7). Calculated for C28H21N5O2:
M 459.51.
(E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-1-(furan-2-
yl)prop-2-en-1-one (6b). Yield 90%, mp 142–144°C.
IR spectrum, ν, cm–1: 3022 (C–Harom), 1690 (C=O),
1
1560 (C=C). H NMR spectrum, δ, ppm: 7.09–8.17 m
(15H, Harom, CH=CH), 9.35 s (1H, 5-H). 13C NMR
spectrum, δC, ppm: 118.2, 120.2, 121.9, 122.8,
123.3, 126.6, 126.8, 127.2, 128.3, 128.5, 128.8, 129.6,
130.4, 131.6, 132.4, 133.3, 134.6, 139.2, 150.4, 151.8,
163.2, 186.6.
{3′-(4-Methoxyphenyl)-1′-phenyl-5-(thiophen-2-
yl)-3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl}(pyr-
idin-4-yl)methanone (8c). Yield 85%, mp 237–239°C.
IR spectrum, ν, cm–1: 3015 (C–Harom), 1601 (C=N),
1567 (C=C). 1H NMR spectrum, δ, ppm: 3.35 d.d (1H,
4-H), 3.84 s (3H, OCH3), 4.12 d.d (1H, 4-H), 5.89 d.d
(1H, 5-H), 7.03–8.77 m (17H, Harom). 13C NMR spec-
trum, δC, ppm: 40.6, 55.8, 61.5, 114.8, 117.2, 119.9,
121.7, 123.2, 124.4, 125.3, 125.8, 126.2, 127.4, 128.5,
129.3, 139.7, 149.7, 155.6, 167.2. Mass spectrum
(ESI), m/z (Irel, %): 505.16 (100.0), 506.16 (31.4),
507.15 (4.5), 507.16 (2.7), 507.16 (2.0), 506.15 (1.8),
508.16 (1.4). Calculated for C29H23N5O2S: M 505.60.
(E)-3-[3-(4-Methoxyphenyl)-1-phenyl-1H-pyra-
zol-4-yl]-1-(thiophen-2-yl)prop-2-en-1-one (6c).
Yield 92%, mp 137–139°C. IR spectrum, ν, cm–1: 3015
1
(C–Harom), 1694 (C=O), 1549 (C=C). H NMR spec-
trum: 3.85 s (3H, OCH3), 7.12–8.13 m (14H, Harom
,
CH=CH), 9.36 s (1H, 5-H). 13C NMR spectrum, δC,
ppm: 56.6, 118.6, 119.7, 121.7, 122.3, 122.8, 126.2,
126.8, 127.5, 128.2, 128.5, 128.6, 129.9, 130.6, 131.7,
132.5, 133.6, 134.4, 139.7, 150.3, 150.6, 163.1, 186.5.
(E)-1-(Furan-2-yl)-3-[3-(4-methoxyphenyl)-1-
phenyl-1H-pyrazol-4-yl]prop-2-en-1-one (6d). Yield
92%, mp 141–143°C. IR spectrum, ν, cm–1: 3017
(C–Harom), 1688 (C=O), 1550 (C=C). 1H NMR spec-
trum, δ, ppm: 3.85 s (3H, OCH3), 7.12–8.14 m (14H,
Harom, CH=CH), 9.35 s (1H, 5-H). 13C NMR spectrum,
{5-(Furan-2-yl)-3′-(4-methoxyphenyl)-1′-phenyl-
3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-
4-yl)methanone (8d). Yield 82%, mp 226–228°C. IR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

SYNTHESIS, CHARACTERIZATION, AND COMPARATIVE STUDY
1799
spectrum, ν, cm–1: 3012 (C–Harom), 1605 (C=N), 1561
(C=C). 1H NMR spectrum, δ, ppm: 3.37 d.d (1H, 4-H),
3.82 s (3H, OCH3), 4.12 d.d (1H, 4-H), 5.84 d.d (1H,
5-H), 7.03–8.76 m (17H, Harom). 13C NMR spectrum,
δC, ppm: 38.1, 56.5, 109.4, 109.9, 117.2, 119.9, 121.7,
123.2, 126.2, 127.5, 128.7, 129.2, 133.2, 139.7, 140.8,
141.7, 142.1, 149.7, 149.9, 167.2. Mass spectrum
(ESI), m/z (Irel, %): 459.17 (100.0), 460.17 (30.3),
461.18 (2.7), 460.17 (1.8), 461.18 (1.7). Calculated for
C29H23N5O3: M 459.54.
{5-(Furan-2-yl)-3′-(4-methoxyphenyl)-1′-phenyl-
3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-
3-yl)methanone (9d). Yield 82%, mp 236–238°C. IR
spectrum, ν, cm–1: 3017 (C–Harom), 1696 (C=N), 1552
(C=C). 1H NMR spectrum, δ, ppm: 3.44 d.d (1H, 4-H),
3.84 s (3H, OCH3), 4.16 d.d (1H, 4-H), 5.92 d.d (1H,
5-H), 7.04–8.76 m (17H, Harom). 13C NMR spectrum,
δC, ppm: 38.1, 55.8, 58.7, 109.4, 109.4, 109.9, 114.8,
117.2, 119.9, 121.7, 123.2, 125.3, 126.2, 128.5, 129.3,
130.7, 135.3, 139.7, 140.8, 141.7, 142.1, 148.1, 148.7,
155.6, 160.6, 167.2. Mass spectrum (ESI), m/z (Irel, %):
489.18 (100.0), 490.18 (31.4), 491.19 (4.7), 490.18
(1.8). Calculated for C29H23N5O3: M 489.18.
{1,3′-Diphenyl-5-(thiophen-2-yl)-3,4-dihydro-
1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-3-yl)metha-
none (9a). Yield 87%, mp 233–235°C. IR spectrum, ν,
cm–1: 3017 (C–Harom), 1695 (C=N), 1550 (C=C).
1H NMR spectrum, δ, ppm: 3.36 d.d (1H, 4-H),
4.07 d.d (1H, 4-H), 5.82 d.d (1H, 5-H), 6.93–9.02 m
(18H, Harom). 13C NMR spectrum, δC, ppm: 40.6, 61.1,
117.2, 119.9, 123.2, 124.4, 125.1, 125.8, 126.2, 127.2,
127.4, 127.5, 128.7, 129.2, 129.3, 129.9, 130.7, 133.2,
135.7, 139.7, 148.1, 148.7, 149.9, 155.6, 167.2. Mass
spectrum (ESI), m/z (Irel, %): 475.15 (100.0), 476.15
(30.3), 477.14 (4.5), 477.15 (2.7), 476.14 (1.8),
477.15 (1.7), 478.15 (1.4). Calculated for C28H21N5OS:
M 475.57.
ACKNOWLEDGMENTS
The authors are thankful to the Head, Department of
Chemistry, M.G. Science Institute, Gujarat University,
Ahmedabad, for providing research facilities.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
{5-(Furan-2-yl)-1′,3′-diphenyl-3,4-dihydro-
1′H,2H-[3,4′-bipyrazol]-2-yl}(pyridin-3-yl)metha-
none (9b). Yield 84%, mp 226–228°C. IR spectrum, ν,
cm–1: 3017 (C–Harom), 1695 (C=N), 1550 (C=C).
1H NMR spectrum, δ, ppm: 3.44 d.d (1H, 4-H),
4.16 d.d (1H, 4-H), 5.92 d.d (1H, 5-H), 7.10–9.02 m
(18H, Harom). 13C NMR spectrum, δC, ppm: 38.1, 55.8,
58.7, 109.4, 109.4, 109.9, 114.8, 117.2, 119.9, 121.7,
123.2, 125.3, 126.2, 128.5, 129.3, 130.7, 135.3, 139.7,
140.8, 141.7, 142.1, 148.1, 148.7, 155.6, 160.6, 167.2.
Mass spectrum (ESI), m/z (Irel, %): 459.17 (100.0),
460.17 (30.3), 461.18 (2.7), 460.17 (1.8), 461.18 (1.7).
Calculated for C28H21N5O2: M 459.51,
1. Vitaku, E., Smith, D., and Njardarson, J., J. Med. Chem.,
2014, vol. 57, p. 10257.
https://doi.org/10.1021/jm501100b
2. Sinha, N., Jain, S., Tilekar, A., Upadhayaya, R.S.,
Kishore, N., Jana, G.H., and Arora, S.K., Bioorg. Med.
Chem. Lett., 2005, vol. 15, p. 1573.
https://doi.org/10.1016/j.bmcl.2005.01.073
3. Bayrak, H., Demirbas, A., Demirbas, N., and Kara-
oglu, S.A., Eur. J. Med. Chem., 2009, vol. 44, p. 4362.
https://doi.org/10.1016/j.ejmech.2009.05.022
4. Jaju, S., Palkar, M., Maddi, V., Ronad, P., Mamle-
desai, S., Satyanarayana, D., and Ghatole, M., Arch.
Pharm. (Weinheim, Ger.), 2009, vol. 342, p. 723.
https://doi.org/10.1002/ardp.200900001
5. Judge, V., Narasimhan, B., Ahuja, M., Sriram, D.,
Yogeeswari, P., de Clercq, E., Pannecouque, C., and
Balzarini, J., Med. Chem. Res., 2011, vol. 21, p. 1451.
https://doi.org/10.1007/s00044-011-9662-9
6. Desai, N.C., Kotadiya, G.M., and Trivedi, A.R., Bioorg.
Med. Chem. Lett., 2014, vol. 24, p. 3126.
{3′-(4-Methoxyphenyl)-1′-phenyl-5-(thiophen-2-
yl)-3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl}(pyri-
din-3-yl)methanone (9c). Yield 86%, mp 237–239°C.
IR spectrum, ν, cm–1: 3017 (C–Harom), 1695 (C=N),
1550 (C=C). 1H NMR spectrum, δ, ppm: 3.36 d.d (1H,
4-H), 3.84 s (3H, OCH3), 4.13 d.d (1H, 4-H), 5.84 d.d
(1H, 5-H), 7.03–8.76 m (18H, Harom). 13C NMR spec-
trum, δC, ppm: 38.1, 55.8, 58.7, 109.4, 109.4, 109.9,
114.8, 117.2, 119.9, 121.7, 123.2, 125.3, 126.2, 128.5,
129.3, 130.7, 135.3, 139.7, 140.8, 141.7, 142.1, 148.1,
148.7, 155.6, 160.6, 167.2. Mass spectrum (ESI),
m/z (Irel, %): 505.16 (100.0), 506.16 (31.4), 507.15
(4.5), 507.16 (2.7), 507.16 (2.0), 506.15 (1.8), 508.16
(1.4). Calculated for C29H23N5O2S: M 505.60.
https://doi.org/10.1016/j.bmcl.2014.05.002
7. Barakat, A., Soliman, M., Al-Majid, A.M., Lotfy, G.,
Ghabbour, H.A., Fun, H.-K., Yousuf, S., Choudhary, M.I.,
and Wadood, A., J. Mol. Struct., 2015, vol. 1098, p. 365.
https://doi.org/10.1016/j.molstruc.2015.06.037
8. Hanna, M.M., Eur. J. Med. Chem., 2012, vol. 55, p. 12.
https://doi.org/10.1016/j.ejmech.2012.06.048
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

ZALA et al.
1800
9. Kaur, H., Machado, M., Kock, C., Smith, P., Chibale, K.,
Prudêncio, M., and Singh, K., Eur. J. Med. Chem., 2015,
vol. 101, p. 266.
13. Performance Standards for Antimicrobial Susceptibility
Testing: Twelfth Informational Supplement (2002)
NCCLS (National Committee for Clinical Laboratory
Standards). ISBN 1-56238454-6. M100-S12 (M7)
https://doi.org/10.1016/j.ejmech.2015.06.045
10. Yadlapalli, R.K., Chourasia, O.P., Vemuri, K.,
Sritharan, M., and Perali, R.S., Bioorg. Med. Chem.
Lett., 2012, vol. 22, p. 2708.
14. Patel, H.B., Gohil, J.D., and Patel, M.P., Monatsh.
Chem., 2017, vol. 148, p. 1057.
https://doi.org/10.1007/s00706-016-1875-7
https://doi.org/10.1016/j.bmcl.2012.02.1
15. Kalaria, P.N., Makawana, J.A., Satasia, S.P.,
Raval, D.K., and Zhu, H.-L., Med. Chem. Commun.,
2014, vol. 5, p. 1555.
11. Bariwal, J.J., Malhotra, M., Molnar, J., Jain, K.S.,
Shah, A.K., and Bariwal, J.B., Med. Chem. Res., 2012,
vol. 21, p. 4002.
https://doi.org/10.1039/C4MD00238E
https://doi.org/10.1007/s00044-011-9925-5
12. Kira, M.A., Abdel-Rahman, M.O., and Gadalla, K.Z.,
Tetrahedron Lett., 1969, vol. 10, p. 109.
16. Sharma, P.K., Kumar, S., Kumar, P., Kaushik, P.,
Kaushik, D., Dhingra, Y., and Aneja, K.R., Eur. J. Med.
Chem., 2010, vol. 45, p. 2650.
https://doi.org/10.1016/S0040-4039(01)88217-4
https://doi.org/10.1016/j.ejmech.2010.01.059
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020