Synthesis and antimicrobial activity of some novel quinoline-pyrazoline-based coumarinyl thiazole derivatives

Article abstract of DOI:10.1007/s00044-017-1855-4

A series of novel 3-(2-(5-(2-chloroquinolin-3-yl)-3-substituted phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-H/halo-2H-chromen-2-ones (9a–9y) was prepared as antimicrobial agents by the condensation of 3-(2-bromoacetyl)-6-H/halo-2H-chromen-2-ones (4

Full text of DOI:10.1007/s00044-017-1855-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-017-1855-4
ORIGINAL RESEARCH
Synthesis and antimicrobial activity of some novel quinoline-
pyrazoline-based coumarinyl thiazole derivatives
Mohd. Imran Ansari1 Suroor Ahmad Khan2
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Received: 9 July 2015 / Accepted: 2 March 2017
© Springer Science+Business Media New York 2017
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Abstract A series of novel 3-(2-(5-(2-chloroquinolin-3-yl)-
3-substituted phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-
4-yl)-6-H/halo-2H-chromen-2-ones (9a–9y) was prepared
as antimicrobial agents by the condensation of 3-(2-bro-
moacetyl)-6-H/halo-2H-chromen-2-ones (4a–4e) and 5-(2-
chloroquinolin-3-yl)-3-substituted phenyl-4,5-dihydro-1H-
pyrazole-1-carbothiamide (8a–8e) in ethanol. The structures
of these compounds were confirmed on the basis of their
infrared, 1H-nuclear magnetic resonance, 13C-nuclear
magnetic resonance, mass and elemental analysis data.
The antimicrobial activity of these compounds was deter-
mined by the serial plate dilution method. The compounds
with fluoro-substituted coumarin ring along with the fluoro-
substituted phenyl ring, 9q, 9r, and 9s, produced better and
potent antimicrobial activity than their corresponding H/
chloro/iodo/bromo-substituted analogs with statistically
significant results (p < 0.05). The compounds 9q and 9r
also produced higher antifungal activity than standard drug
ketoconazole against Penicillium citrinum. However, these
compounds required higher concentration than standard
drugs, ofloxacin, and ketoconazole, to produce these effects.
The structural modification of these compounds may
enhance their potency as antimicrobial agents, but this
requires further studies.
Keywords Coumarin Thiazole Quinoline Pyrazoline
Antimicrobial
Introduction
Antimicrobial resistance was first reported in the 1940s. It is
the resistance developed by a microorganism for an anti-
microbial agent against, which it was originally sensitive.
Infection caused by a resistant microorganism often fails to
respond to conventional treatment, resulting in prolonged
illness, higher risk of death and greater costs (Jindal et al.
2015). Today antimicrobial resistance has become a global
concern because in the modern era of travel and trade,
resistant organisms rapidly cross the man-made boundaries
through humans or the food chain (Jindal et al. 2015; Bhatia
2013). Studies have revealed that the cause of antibiotic
resistance includes the irrational use of antibiotics and failure
to discover new antimicrobial agents since the second half of
1980s. Accordingly, development of new antimicrobial
agents is the need of today to combat antimicrobial resistance
(Jindal et al. 2015; Bhatia 2013; Brandt et al. 2014).
Coumarinyl heterocycles, thiazolyl heterocycles, quinoli-
nyl heterocycles, and pyrazolinyl heterocycles have an
important place in medicinal chemistry. Recently, review
articles mentioning the usefulness of coumarinyl heterocyles
(Jayashree et al. 2014; Xin-Mei et al. 2013; Venugopala et al.
2013), thiazolyl heterocycles (Kashyap et al. 2012; Mishra
et al. 2015; Leoni et al. 2014a; Leoni et al. 2014b), quinolinyl
heterocycles (Kumar et al. 2009; Marella et al. 2013b; Kaur
et al. 2010), and pyrazolinyl heterocycles (Alex and Kumar
2014; Marella et al. 2013a) as analgesic, anti-inflammatory,
antibacterial, antifungal, antiviral, antiparasitic, antic-
oagulant, anti-Alzheimer’s disease, anti-Parkinson’s Disease,
* Mohd. Imran Ansari
imran_inderlok@yahoo.co.in
Suroor Ahmad Khan
sakhan_pchem@yahoo.co.in
1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Northern Border University, P.O. Box 840, Rafha 91911, Saudi
Arabia
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Jamia Hamdard (Hamdard University), New Delhi 110062, India

Med Chem Res
anticancer, antioxidants, antidiabetic, Central Nervous Sys-
tem depressant, and antimalarial have been published.
Among these, coumarinyl thiazoles have also been reported
to possess different biological activities like antimicrobial
(Shaaban et al. 2012; Vijesh et al. 2010; Bondock et al. 2013;
Chimenti et al. 2011; Arshad et al. 2011; Abd El-Wahab
et al. 2014; Venugopala and Jayashree 2008; Rao et al. 2008;
Venugopala et al. 2008), anticancer (Gali et al. 2015), anti-
oxidant (Thota et al. 2015), anticonvulsant (Siddiqui et al.
2009; Amin et al. 2008), anti-tubercular (Karalı et al. 2002;
Gursoy and Karali 2003), anti-inflammatory (Kalkhambkar
et al. 2007; Aggarwal et al. 2013; Venugopala et al. 2004;
Jayashree et al. 2005), analgesic (Venugopala and Jayashree
2003), and anticholinesterase activities (Kurt et al. 2015).
Recently, coumarinyl thiazole moiety attached with
pyrazoline ring (I) and quinoline-pyrazoline-based thiazoles
(II) have been postulated as templates and lead compounds
for the development of new antimicrobial agents (Aggarwal
et al. 2013; Desai et al. 2013a) (Fig. 1).
Encouraged by these observations and in continuation of
our search for potent heterocyclic biological agents (Imran
and Khan 2004b; Khan et al. 2005; Alam et al. 2005a; Alam
et al. 2005b; Gupta et al. 2005; Alam et al. 2010; Gilani and
Khan 2013; Kaushik et al. 2012; Gilani et al. 2010)
including coumarinyl heterocycles (Imran and Khan 2004a)
and thiazolyl heterocycles (Imran et al. 2009), we decided
to prepare some novel quinoline-pyrazoline-based coumar-
inyl thiazoles (9a–9y), herein after the targeted compounds
(9a–9y), as potent antimicrobial agents.
Material and methods
General
Melting points were measured in open capillary tubes and
are uncorrected. Infrared (IR) (KBr) spectra were recorded
on a Nicolet, 5PC FT-IR spectrometer (Browser Morner,
USA). 1H-nuclear magnetic resonance (NMR) and 13C-
NMR spectra were recorded on a Bruker DRX-300 FT
NMR (Bruker, Germany) spectrophotometer using Tetra-
methylsilane as internal reference (chemical shift in δ ppm).
Mass spectra were recorded on a Jeol-JMS-D-300 mass
spectrometer (70 eV) (Jeol, Japan). Satisfactory analysis for
C, H, and N was obtained for the compounds within 0.4%
of the theoretical values. The Purity of the compounds was
checked on silica gel G plates using iodine vapors as
visualizing agent. The Rf value of the compounds was
determined by using a mixture of toluene, ethyl acetate and
formic acid (5:4:1). All reagents used in the present work
were of analytical grade.
Synthesis of the targeted compounds (9a–9y)
General procedure for the synthesis of 3-acetyl-6-H/halo-
2H-chromen-2-one (3a–3e)
An equimolar mixture of appropriate salicyldehyde (1a–1e)
and ethyl acetoacetate (2) was stirred in 20 mL of ethanol in
the presence of piperidine (0.2 mL) for about 1 to 2 h.
Fig. 1 Structures of postulated
antimicrobial lead compounds, I
and II, and synthesized
compounds (9a–9y)

Med Chem Res
The mixture was cooled, the solid was separated and
recrystallized from ethanol.
of formula (7a–7e) (Desai et al. 2013a; Abdel-Sattar 2008)
were prepared by the method described in the literature. The
5-(2-chloroquinolin-3-yl)-3-substituted phenyl-4,5-dihydro-
1H-pyrazole-1-carbothiamides of formula (8a–8e) were also
prepared according to the method provided in the literature
(Desai et al. 2013a).
The detailed characterization data of the compounds
(8a–8e) is also provided in the literature (Desai et al.
2013a).
The detailed characterization data of (3a–3d) is provided
in the literature (Gali et al. 2015; Siddiqui et al. 2009;
Gursoy and Karali 2003; Aggarwal et al. 2013; Jayashree
et al. 2005; Venugopala and Jayashree 2003; Chopra et al.
2006; Kumar et al. 2011; Abdel-Sattar 2008).
3-Acetyl-6-iodo-2H-chromen-2-one (3e) It was obtained
from the reaction of 5-iodosalicyldehyde (1e) and ethyl
acetoacetate (2) as yellowish brown crystals (EtOH). Yield
80%; m.p. 202–205 °C; IR (KBr) νmax 1725 and 1710
3-(2-Chlorophenyl)-5-(2-chloroquinolin-3-yl)-4,5-dihydro-
1H-pyrazole-1-carbothioamide (8a)
1
(C=O), 1608 (C=C), 1230 (C–O–C), 560 (C–I); H NMR
(DMSO-d6, 400 MHz): δ = 2.55 (s, 3H, –COCH3),
7.30–7.90 (m, 3H, Ar–H), 8.24 (s, 1H, C4–H); Mass (m/z)
314 (M+); Anal. Calcd for C11H7IO3: C, 42.07; H, 2.25;
N, 0.0. Found: C, 42.03; H, 2.24; N, 0.0.
It was obtained by the reaction of the compound (7a) with
thiosemicarbazide as faint gray crystals (EtOH).Yield 75%;
m.p. 174–176 °C; IR (KBr) νmax 3455 (N–H), 1570 (C=N),
1520 (C=C), 1330 (C=S); Anal. Calcd for C19H14Cl2N4S:
C, 56.87; H, 3.52; N, 13.96. Found: C, 56.85; H, 3.48;
N, 13.90.
General procedure for the synthesis of 3-(2-bromoacetyl)-6-
H/halo-2H-chromen-2-one (4a–4e)
To a mixture of appropriate compound (3a–3e) (0.25 moles)
in 200 mL of alcohol free chloroform, bromine (0.30 moles)
in 25 mL of chloroform was added drop wise with stirring.
The reaction mixture was first stirred for 1 h at room tem-
perature and then it was refluxed for about 30 min. The
reaction mixture was cooled, solid mass was separated,
washed with diethyl ether and recrystallized from acetic
acid.
The detailed characterization data of (4a–4d) is provided
in the literature (Gali et al. 2015; Siddiqui et al. 2009;
Gursoy and Karali 2003; Aggarwal et al. 2013; Jayashree
et al. 2005; Venugopala and Jayashree 2003; Chopra et al.
2006; Desai et al. 2013b).
5-(2-Chloroquinolin-3-yl)-3-(2-fluorophenyl)-4,5-dihydro-
1H-pyrazole-1-carbothioamide (8b)
It was obtained by the reaction of the compound (7b) with
thiosemicarbazide as faint brown crystals (EtOH). Yield
70%; m.p. 179–181 °C; IR (KBr) νmax 3458 (N–H), 1583
(C=N), 1521 (C=C), 1333 (C=S); Anal. Calcd for
C19H14ClFN4S: C, 59.30; H, 3.67; N, 14.51. Found:
C, 59.25; H, 3.66; N, 14.51.
5-(2-Chloroquinolin-3-yl)-3-(3-fluorophenyl)-4,5-dihydro-
1H-pyrazole-1-carbothioamide (8c)
3-(2-bromoacetyl)-6-iodo-2H-chromen-2-one (4e) It was
obtained by the reaction of the compound (3e) with bromine
as faint yellowish needles (CH3COOH).Yield 60%; m.p.
188–192 °C;°C; IR (KBr) νmax 1722 and 1690 (C=O), 1604
It was obtained by the reaction of the compound (7c) with
thiosemicarbazide as faint pink crystals (EtOH). Yield 75%;
m.p. 167–169 °C; IR (KBr) νmax 3465 (N-H), 1578 (C=N),
1522 (C=C), 1330 (C=S); Anal. Calcd for C19H14ClFN4S:
C, 59.30; H, 3.67; N, 14.56. Found: C, 59.24; H, 3.63;
N, 14.50.
1
(C=C), 1232 (C–O–C), 685 (C–Br), 560 (C–I); H NMR
(DMSO-d6, 400 MHz): δ = 4.55 (s, 2H, –COCH2Br),
7.30–8.04 (m, 3H, Ar–H), 8.28 (s, 1H, C4–H); Mass (m/z):
392 (M+); Anal. Calcd for C11H6BrIO3: C, 33.62; H, 1.54;
N, 0.0. Found: C, 33.60; H, 1.51; N, 0.0.
5-(2-Chloroquinolin-3-yl)-3-(4-fluorophenyl)-4,5-dihydro-
1H-pyrazole-1-carbothioamide (8d)
General procedure for the synthesis of 5-(2-chloroquinolin-
3-yl)-3-substituted phenyl-4,5-dihydro-1H-pyrazole-1-
carbothiamide (8a–8e)
It was obtained by the reaction of the compound (7d) with
thiosemicarbazide as faint reddish-brown crystals (EtOH).
Yield 76%; m.p. 208–210 °C; IR (KBr) νmax 3470 (N–H),
1585 (C=N), 1523 (C=C), 1336 (C=S); Anal. Calcd for
C19H14ClFN4S: C, 59.30; H, 3.67; N, 14.56. Found:
C, 59.22; H, 3.64; N, 14.53.
The starting materials for the preparation of the compounds
(8a–8e) namely, 2-Chloroquinoline-3-carbaldehyde of for-
mula 5 (Desai et al. 2013a; Kumar et al. 2010) and 3-(2-
chloroquinolin-3-yl)-1-substituted phenylprop-2-en-1-ones

Med Chem Res
5-(2-Chloroquinolin-3-yl)-3-(4-nirophenyl)-4,5-dihydro-
1H-pyrazole-1-carbothioamide (8e)
(d, J = 17 Hz, 1H, C4–H pyrazoline), 3.86 (d, J = 17 Hz,
1H, C4–H pyrazoline), 5.78 (d, J = 18 Hz, 1H, C5–H pyr-
azoline), 7.33–8.07 (m, 13H, Ar–H), 8.20 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 116.6 (Ar–C), 117.1
(Ar–C), 119.2 (Ar–C), 121.9 (Ar–C), 125.4 (Ar–C), 126.4
(Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C), 128.5
(Ar–C), 128.9 (Ar–C), 129.3 (Ar–C), 130.4 (Ar–C), 130.9
(Ar–C), 131.8 (Ar–C), 131.9 (Ar–C), 133.6 (Ar–C), 137.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 154.0 (Ar–C), 157.6 (Ar–C), 162.9
(C=O carbon of coumarin ring), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 552 (M+); Anal. Calcd for
C30H18ClFN4O2S: C, 65.16; H, 3.28; N, 10.13. Found:
C, 65.10; H, 3.25; N, 10.10.
It was obtained by the reaction of the compound (7e) with
thiosemicarbazide as orange crystals (EtOH). Yield 70%;
m.p. 223–225 °C; IR (KBr) νmax 3470 (N–H), 1584
(C=N), 1515 (C=C), 1328 (C=S); Anal. Calcd for
C19H14ClN5O2S: C, 55.41; H, 3.43; N, 17.00. Found:
C, 55.35; H, 3.40; N, 16.94.
General procedure for the synthesis of 3-(2-(5-(2-
chloroquinolin-3-yl)-3-substituted phenyl-4,5-dihydro-1H-
pyrazol-1-yl)thiazol-4-yl)-6-H/halo-2H-chromen-2-ones
(9a–9y)
To a mixture of the appropriate compound (8a–8e) (0.01
mole) in ethanol (99.9%), respective compound (4a–4e)
(0.01 mole) was added and the resulting mixture was heated
to reflux for about 1 to 3 h. The mixture was cooled,
the solid was separated and washed with 10% ethanol.
The products were recrystallized from ethanol.
3-(2-(5-(2-chloroquinolin-3-yl)-3-(3-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
(9c) It was obtained by the reaction of the compound (4a)
with the compound (8c) as faint yellow crystals (EtOH).
Yield 78%; m.p. 210–212 °C; Rf value 0.66; IR (KBr) νmax
1721 (C=O), 1580 (C=N), 1535 (C=C), 1261 (C–O–C),
3-(2-(3-(2-Chlorophenyl)-5-(2-chloroquinolin-3-yl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
(9a) It was obtained by the reaction of the compound (4a)
with the compound (8a) as yellowish-brown crystals
(EtOH). Yield 75%; m.p. 238–240 °C; Rf value 0.58; IR
(KBr) νmax 1715 (C=O), 1578 (C=N), 1535 (C=C), 1255
(C–O–C), 1108 (C–S); 1HNMR (DMSO-d6, 400 MHz):δ =
3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.83 (d, J = 17
Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.35–8.05 (m, 13H, Ar–H), 8.18 (s, 1H, C5–H
thiazole), 8.54 (s, 1H, C4–H coumarin); 13CNMR (DMSO-
d6, 100 MHz):δ = 40.0 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 117.1 (Ar–C), 121.9
(Ar–C), 126.4 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 128.9 (Ar–C), 129.3 (Ar–C), 129.8
(Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.1 (Ar–C), 131.3
(Ar–C), 131.6 (Ar–C), 131.9 (Ar–C), 133.4 (Ar–C), 137.2
(Ar–C), 138.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 154.0, 162.9
(C=O carbon of coumarin ring), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z) 568 (M+); Anal. Calcd for
C30H18Cl2N4O2S: C, 63.28; H, 3.19; N, 9.84. Found: C,
63.20; H, 3.15; N, 9.79.
1
1112 (C–S); H NMR (DMSO-d6, 400 MHz): δ = 3.59 (d,
J = 17 Hz, 1H, C4–H pyrazoline), 3.87 (d, J = 17 Hz, 1H,
C4–H pyrazoline), 5.75 (d, J = 18 Hz, 1H, C5–H pyrazo-
line), 7.31–8.05 (m, 13H, Ar–H), 8.19 (s, 1H, C5–H thia-
zole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-d6,
100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5 of
the pyrazoline ring), 114.5 (Ar–C), 115.0 (Ar–C), 117.1
(Ar–C), 118.8 (Ar–C), 121.9 (Ar–C), 124.8 (Ar–C), 126.4
(Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C), 128.5
(Ar–C), 128.9 (Ar–C), 129.3 (Ar–C), 130.4 (Ar–C), 130.9
(Ar–C), 131.4 (Ar–C), 131.9 (Ar–C), 136.6 (Ar–C), 137.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 154.0 (Ar–C), 162.9 (C=O carbon
of coumarin ring), 164.0 (Ar–C), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 552 (M+); Anal. Calcd for
C30H18ClFN4O2S: C, 65.16; H, 3.28; N, 10.13. Found:
C, 65.12; H, 3.27; N, 10.11.
3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
(9d) It was obtained by the reaction of the compound (4a)
with the compound (8d) as yellow crystals (EtOH). Yield
75%; m.p. 226–228 °C; Rf value 0.69; IR (KBr) νmax 1713
(C=O), 1586 (C=N), 1530 (C=C), 1255 (C–O–C), 1114
3-(2-(5-(2-chloroquinolin-3-yl)-3-(2-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
(9b) It was obtained by the reaction of the compound (4a)
with the compound (8b) as reddish-yellow crystals (EtOH).
Yield 60%; m.p. 220–222 °C; Rf value 0.64; IR (KBr) νmax
1718 (C=O), 1578 (C=N), 1533 (C=C), 1266 (C–O–C),
1111 (C–S); 1H NMR (DMSO-d6, 400 MHz): δ = 3.57
1
(C–S); H NMR (DMSO-d6, 400 MHz): δ = 3.59 (d, J =
17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J = 17 Hz, 1H, C4–H
pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H pyrazoline),
7.30–8.01 (m, 13H, Ar–H), 8.18 (s, 1H, C5–H thiazole),
8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-d6, 100
MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5 of the

Med Chem Res
pyrazoline ring), 114.5 (Ar–C), 116.6 (2C, Ar–C), 117.1
(Ar–C), 121.9 (Ar–C), 126.4 (Ar–C), 127.6 (Ar–C), 128.0
(Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 128.9 (Ar–C), 129.3
(Ar–C), 130.4 (Ar–C), 130.5 (2C, Ar–C), 130.9 (Ar–C),
131.9 (Ar–C), 133.0 (Ar–C), 137.2 (Ar–C), 145.9 (Ar–C),
146.4 (Ar–C), 147.1 (Ar–C), 152.7 (Ar–C), 152.9 (Ar–C),
154.0 (Ar–C), 162.9 (C=O carbon of coumarin ring), 166.2
(Ar–C), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
552 (M+); Anal. Calcd for C30H18ClFN4O2S: C, 65.16; H,
3.28; N, 10.13. Found: C, 65.11; H, 3.22; N, 10.12.
(C=O carbon of coumarin ring), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 602 (M+); Anal. Calcd For
C30H17Cl3N4O2S: C, 59.67; H, 2.84; N, 9.28. Found:
C, 59.65; H, 2.79; N, 9.25.
6-Chloro-3-(2-(5-(2-chloroquinolin-3-yl)-3-(2-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9g) It was obtained by the reaction of the
compound (4b) with the compound (8b) as creamy yellow
crystals (EtOH). Yield 80%; m.p. 240–242 °C; Rf value
0.66; IR (KBr) νmax 1723 (C=O), 1582 (C=N), 1533
3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-nitrophenyl)-4,5-dihy-
dro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
(9e) It was obtained by the reaction of the compound (4a)
with the compound (8e) as reddish-brown crystals (EtOH).
Yield 78%; m.p. 238–240 °C; Rf value 0.71; IR (KBr) νmax
1717 (C=O), 1579 (C=N), 1534(C=C), 1258 (C–O–C),
1
(C=C), 1255 (C–O–C), 1108 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.59 (d, J = 17 Hz, 1H, C4-H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.76 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.32–8.08 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin);
13C NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyr-
azoline ring), 56.4 (C5 of the pyrazoline ring), 114.5
(Ar–C), 116.6 (Ar–C), 119.0 (Ar–C), 119.2 (Ar–C), 124.6
(Ar–C), 125.4 (Ar–C), 127.6 (Ar–C), 127.8 (Ar–C), 128.0
(Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.5
(Ar–C), 130.9 (Ar–C), 131.8 (Ar–C), 131.9 (Ar–C), 132.0
(Ar–C), 133.6 (Ar–C), 137.2 (Ar–C), 145.9 (Ar–C), 146.4
(Ar–C), 147.1 (Ar–C), 152.1 (Ar–C), 152.7 (Ar–C), 152.9
(Ar–C), 160.6 (Ar–C), 162.9 (C=O carbon of coumarin
ring), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
586 (M+); Anal. Calcd for C30H17Cl2FN4O2S): C, 61.34;
H, 2.92; N, 9.54. Found: C, 61.30; H, 2.90; N, 9.51.
1
1105 (C–S); H NMR (DMSO-d6, 400 MHz): δ = 3.61 (d,
J = 17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J = 17 Hz, 1H,
C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H pyrazo-
line), 7.30–8.05 (m, 13H, Ar–H), 8.20 (s, 1H, C5–H thia-
zole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-d6,
100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5 of
the pyrazoline ring), 114.5 (Ar–C), 117.1 (Ar–C), 121.9
(Ar–C), 126.4 (Ar–C), 127.6 (Ar–C), 128.0 (3C, Ar–C),
128.3 (Ar–C), 128.5 (Ar–C), 128.7 (2C, Ar–C), 128.9
(Ar–C), 129.3 (Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.9
(Ar–C), 137.2 (Ar–C), 143.5 (Ar–C), 145.9 (Ar–C), 146.4
(Ar–C), 147.1 (Ar–C), 151.2 (Ar–C), 152.7 (Ar–C), 152.9
(Ar–C), 154.0 (Ar–C), 162.9 (C=O carbon of coumarin
ring), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
579 (M+); Anal. Calcd for C30H18ClN5O4S: C, 62.12; H,
3.13; N, 12.07. Found: C, 62.10; H, 3.10; N, 12.00.
6-Chloro-3-(2-(5-(2-chloroquinolin-3-yl)-3-(3-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9h) It was obtained by the reaction of the
compound (4b) with the compound (8c) as faint yellow
crystals (EtOH). Yield 70%; m.p. 250–252 °C; Rf value
0.64; IR (KBr) νmax 1719 (C=O), 1578 (C=N), 1533
6-Chloro-3-(2-(3-(2-chlorophenyl)-5-(2-chloroquinolin-3-
yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-
2-one (9f) It was obtained by the reaction of the compound
(4b) with the compound (8a) as yellowish crystals (EtOH).
Yield 75%; m.p. 254–256 °C; Rf value 0.71; IR (KBr) νmax
1722 (C=O), 1580 (C=N), 1538 (C=C), 1260 (C–O–C),
1
(C=C), 1258 (C–O–C), 1110 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.59 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.76 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.30–8.04 (m, 12H, Ar–H), 8.19
(s, 1H, C5–H thiazole), 8.54 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 115.0
(Ar–C), 118.8 (Ar–C), 119.0 (Ar–C), 124.6 (Ar–C), 124.8
(Ar–C), 127.6 (Ar–C), 127.8 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.5 (Ar–C), 130.9
(Ar–C), 131.4 (Ar–C), 131.9 (Ar–C), 132.0 (Ar–C), 136.6
(Ar–C), 137.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 152.1 (Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 162.9
(C=O carbon of coumarin ring), 164.0 (Ar–C), 168.3
(C5 carbon of the thiazole ring); Mass (m/z): 586 (M+);
Anal. Calcd for C30H17Cl2FN4O2S: C, 61.34; H, 2.92; N,
9.54. Found: C, 61.32; H, 2.91; N, 9.50.
1
1118 (C–S); H NMR (DMSO-d6, 400 MHz): δ = 3.58 (d,
J = 17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J = 17 Hz, 1H,
C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H pyrazo-
line), 7.31–8.09 (m, 12H, Ar–H), 8.17 (s, 1H, C5–H thia-
zole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-d6,
100 MHz): δ = 40.0 (C4 of the pyrazoline ring), 56.4 (C5 of
the pyrazoline ring), 114.5 (Ar–C), 119.0 (Ar–C), 124.6
(Ar–C), 127.6 (Ar–C), 127.8 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 129.8 (Ar–C), 130.4 (Ar–C), 130.5
(Ar–C), 130.9 (Ar–C), 131.1 (Ar–C), 131.3 (Ar–C), 131.6
(Ar–C), 131.9 (Ar–C), 132.0 (Ar–C), 133.4 (Ar–C), 137.2
(Ar–C), 138.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 152.1 (Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 162.9

Med Chem Res
6-Chloro-3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9i) It was obtained by the reaction of the
compound (4b) with the compound (8d) as orange crystals
(EtOH). Yield 75%; m.p. 235–237 °C; Rf value 0.69; IR
(KBr) νmax 1720 (C=O), 1585 (C=N), 1533 (C=C), 1260
400 MHz): δ = 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.30–8.05 (m, 12H, Ar–H), 8.20
(s, 1H, C5–H thiazole), 8.54 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.0 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 119.2
(Ar–C), 120.8 (Ar–C), 125.4 (Ar–C), 127.6 (Ar–C), 128.0
(Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 129.8 (Ar–C), 130.4
(Ar–C), 130.9 (Ar–C), 131.1 (Ar–C), 131.3 (2C, Ar–C),
131.6 (Ar–C), 131.9 (Ar–C), 133.4 (Ar–C), 135.2 (Ar–C),
137.2 (Ar–C), 138.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C),
147.1 (Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 153.0 (Ar–C),
162.9 (C=O carbon of coumarin ring), 168.3 (C5 carbon of
the thiazole ring); Mass (m/z): 646 (M+); Anal. Calcd for
C30H17BrCl2N4O2S: C, 55.58; H, 2.64; N, 8.64. Found:
C, 55.55; H, 2.60; N, 8.61.
1
(C–O–C), 1112 (C–S); H NMR (DMSO-d6, 400 MHz):
δ = 3.55 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.85 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.35–8.05 (m, 12H, Ar–H), 8.18 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 116.6 (2C, Ar–C),
119.0 (Ar–C), 124.6 (Ar–C), 127.6 (Ar–C), 127.8 (Ar–C),
128.0 (Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 130.4 (Ar–C),
130.5 (3C, Ar–C), 130.9 (Ar–C), 131.9 (Ar–C), 132.0
(Ar–C), 133.0 (Ar–C), 137.2 (Ar–C), 145.9 (Ar–C), 146.4
(Ar–C), 147.1 (Ar–C), 152.1 (Ar–C), 152.7 (Ar–C), 152.9
(Ar–C), 162.9 (C=O carbon of coumarin ring), 166.2
(Ar–C), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
586 (M+); Anal. Calcd for C30H17Cl2FN4O2S: C, 61.34; H,
2.92; N, 9.54. Found: C, 61.30; H, 2.88; N, 9.49.
6-Bromo-3-(2-(5-(2-chloroquinolin-3-yl)-3-(2-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9l) It was obtained by the reaction of the
compound (4c) with the compound (8b) as dark yellow
crystals (EtOH). Yield 70%; m.p. 245–247 °C; Rf value
0.72; IR (KBr) νmax 1714 (C=O), 1576 (C=N), 1532
1
6-Chloro-3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-nitrophenyl)-
4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-
one (9j) It was obtained by the reaction of the compound
(4b) with the compound (8e) as brownish-yellow crystals
(EtOH). Yield 65%; m.p. 230–232 °C; Rf value 0.71; IR
(KBr) νmax 1722 (C=O), 1577 (C=N), 1534 (C=C), 1259
(C=C), 1266 (C–O–C), 1110 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.56 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.85 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.32–8.01 (m, 12H, Ar–H), 8.19
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 116.6
(Ar–C), 119.2 (2C, Ar–C), 120.8 (Ar–C), 125.4 (2C,
Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C), 128.5
(Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.3 (Ar–C), 131.8
(Ar–C), 131.9 (Ar–C), 133.6 (Ar–C), 135.2 (Ar–C), 137.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 153.0 (Ar–C), 160.6 (Ar–C), 162.9
(C=O carbon of coumarin ring), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 630 (M+); Anal. Calcd for
C30H17BrClFN4O2S: C, 57.02; H, 2.71; N, 8.87. Found:
C, 56.99; H, 2.67; N, 8.85.
1
(C–O–C), 1116 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.30–8.02 (m, 12H, Ar–H), 8.18 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 117.0 (Ar–C), 124.6
(Ar–C), 127.6 (Ar–C), 127.8 (Ar–C), 128.0 (3C, Ar–C),
128.3 (Ar–C), 128.5 (Ar–C), 128.7 (2C, Ar–C), 130.4
(Ar–C), 130.5 (Ar–C), 130.9 (Ar–C), 131.9 (Ar–C), 132.0
(Ar–C), 137.2 (Ar–C), 143.5 (Ar–C), 145.9 (Ar–C), 146.4
(Ar–C), 147.1 (Ar–C), 151.2 (Ar–C), 152.1 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 162.9 (C=O carbon of coumarin
ring), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
613 (M+); Anal. Calcd for C30H17Cl2N5O4S: C, 58.64; H,
2.79; N, 11.40. Found: C, 58.59; H, 2.75; N, 11.38.
6-Bromo-3-(2-(5-(2-chloroquinolin-3-yl)-3-(3-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9m) It was obtained by the reaction of the
compound (4c) with the compound (8c) as light-yellow
brown crystals (EtOH). Yield 65%; m.p. 230–232 °C; Rf
value 0.65; IR (KBr) νmax 1718 (C=O), 1574 (C=N), 1534
6-Bromo-3-(2-(3-(2-chlorophenyl)-5-(2-chloroquinolin-3-
yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-
2-one (9k) It was obtained by the reaction of the com-
pound (4c) with the compound (8a) as brownish-yellow
crystals (EtOH). Yield 75%; m.p. 255–257 °C; Rf value
0.73; IR (KBr) νmax 1715 (C=O), 1588 (C=N), 1534
(C=C), 1263 (C–O–C), 1114 (C–S) ; 1H NMR (DMSO-d6,
1
(C=C), 1258 (C–O–C), 1115 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.87 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.33–8.05 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.54 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline

Med Chem Res
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 115.0
(Ar–C), 118.8 (Ar–C), 119.2 (Ar–C), 120.8 (Ar–C), 124.8
(Ar–C), 125.4 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.3
(Ar–C), 131.4 (Ar–C), 131.9 (Ar–C), 135.2 (Ar–C), 136.6
(Ar–C), 137.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 153.0 (Ar–C), 162.9
(C=O carbon of coumarin ring), 164.0 (Ar–C), 168.3 (C5
carbon of the thiazole ring); Mass (m/z): 630 (M+); Anal.
Calcd for C30H17BrClFN4O2S: C, 57.02; H, 2.71; N, 8.87.
Found: C, 57.00; H, 2.68; N, 8.84.
(Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 151.2 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 153.0 (Ar–C), 162.9 (C=O carbon
of coumarin ring), 168.3 (C5 carbon of the thiazole ring);
Mass (m/z): 657 (M+); Anal. Calcd for C30H17BrClN5O4S:
C, 54.69; H, 2.60; N, 10.63. Found: C, 54.63; H, 2.55; N,
10.63.
3-(2-(3-(2-Chlorophenyl)-5-(2-chloroquinolin-3-yl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-fluoro-2H-chro-
men-2-one (9p) It was obtained by the reaction of the
compound (4d) with the compound (8a) as yellow crystals
(EtOH). Yield 70%; m.p. 225–227 °C; Rf value 0.73; IR
(KBr) νmax 1720 (C=O), 1580 (C=N), 1533 (C=C), 1266
6-Bromo-3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-fluorophe-
nyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chro-
men-2-one (9n) It was obtained by the reaction of the
compound (4c) with the compound (8d) as light-brown
crystals (EtOH). Yield 68%; m.p. 245–247 °C; Rf value
0.71; IR (KBr) νmax 1719 (C=O), 1578 (C=N), 1534
1
(C–O–C), 1110 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.84 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.31–8.04 (m, 12H, Ar–H), 8.19 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.0 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 115.6 (Ar–C), 116.1
(Ar–C), 124.8 (Ar–C), 126.1 (Ar–C), 127.6 (Ar–C), 128.0
(Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 129.8 (Ar–C), 130.4
(Ar–C), 130.9 (Ar–C), 131.1 (Ar–C), 131.3 (Ar–C), 131.6
(Ar–C), 131.9 (Ar–C), 133.4 (Ar–C), 137.2 (Ar–C), 138.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 147.6
(Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 160.6 (Ar–C), 162.9
(C=O carbon of coumarin ring), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 586 (M+); Anal. Calcd for
C30H17Cl2FN4O2S: C, 61.34; H, 2.92; N, 9.54. Found:
C, 61.30; H, 2.89; N, 9.51.
1
(C=C), 1258 (C–O–C), 1110 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.56 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.85 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.30–8.05 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 116.6
(2C, Ar–C), 119.2 (Ar–C), 120.8 (Ar–C), 125.4 (Ar–C),
127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C), 128.5 (Ar–C),
130.4 (Ar–C), 130.5 (2C, Ar–C), 130.9 (Ar–C), 131.3
(Ar–C), 131.9 (Ar–C), 133.0 (Ar–C), 135.2 (Ar–C), 137.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 153.0 (Ar–C), 162.9 (C=O carbon
of coumarin ring), 166.2 (Ar–C), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 630 (M+); Anal. Calcd for
C30H17BrClFN4O2S: C, 57.02; H, 2.71; N, 8.87. Found: C,
57.00; H, 2.69; N, 8.85.
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(2-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-fluoro-2H-chro-
men-2-one (9q) It was obtained by the reaction of the
compound (4d) with the compound (8b) as faint brownish-
yellow crystals (EtOH). Yield 72%; m.p. 215–217 °C; Rf
value 0.70; IR (KBr) νmax 1719 (C=O), 1578 (C=N), 1532
6-Bromo-3-(2-(5-(2-chloroquinolin-3-yl)-3-(4-nitrophenyl)-
4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-
one (9o) It was obtained by the reaction of the compound
(4c) with the compound (8e) as light reddish-brown yellow
crystals (EtOH). Yield 65%; m.p. 255–257 °C; Rf value
0.69; IR (KBr) νmax 1715 (C=O), 1578 (C=N), 1531
1
(C=C), 1259 (C–O–C), 1114 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.55 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.89 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.33–8.05 (m, 12H, Ar–H), 8.20
(s, 1H, C5–H thiazole), 8.53 (s, 1H, C4–H coumarin), 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 115.6
(Ar–C), 116.1 (Ar–C), 116.6 (Ar–C), 117.2 (Ar–C), 124.8
(Ar–C), 125.4 (Ar–C), 126.1 (Ar–C), 127.6 (Ar–C), 128.0
(Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.9
(Ar–C), 131.8 (Ar–C), 131.9 (Ar–C), 133.6 (Ar–C), 137.2
(Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 149.6
(Ar–C), 152.7 (Ar–C), 152.9 (Ar–C), 160.6 (2C, Ar–C),
162.9 (C=O carbon of coumarin ring), 168.3 (C5 carbon of
the thiazole ring); Mass (m/z): 570 (M+); Anal. Calcd for
1
(C=C), 1259 (C–O–C), 1109 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.57 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.33–8.03 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 119.2
(Ar–C), 120.8 (Ar–C), 125.4 (Ar–C), 127.6 (Ar–C), 128.0
(3C, Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 128.7 (2C,
Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.3 (Ar–C), 131.9
(Ar–C), 135.2 (Ar–C), 137.2 (Ar–C), 143.5 (Ar–C), 145.9

Med Chem Res
C30H17ClF2N4O2S: C, 63.11; H, 3.00; N, 9.81. Found:
C, 63.08; H, 2.97; N, 9.77.
one (9t) It was obtained by the reaction of the compound
(4d) with the compound (8e) as reddish-yellow crystals
(EtOH). Yield 75%; m.p. 255–257 °C; Rf value 0.66; IR
(KBr) νmax 1716 (C=O), 1577 (C=N), 1535 (C=C), 1259
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(3-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-fluoro-2H-chro-
men-2-one (9r) It was obtained by the reaction of the
compound (4d) with the compound (8c) as light-yellow
crystals (EtOH).Yield 77%; m.p. 233–235 °C; Rf value
0.74; IR (KBr) νmax 1717 (C=O), 1577 (C=N), 1533
1
(C–O–C), 1108 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.56 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.31–8.05 (m, 12H, Ar–H), 8.18 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 114.5 (Ar–C), 115.6 (Ar–C), 116.1
(Ar–C), 124.8 (Ar–C), 126.1 (Ar–C), 127.6 (Ar–C), 128.0
(3C, Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 128.7 (2C,
Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.9 (Ar–C), 137.2
(Ar–C), 143.5 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 149.6 (Ar–C), 151.2 (Ar–C), 152.7 (Ar–C), 152.9
(Ar–C), 160.6 (Ar–C), 162.9 (C=O carbon of coumarin
ring), 168.3 (C5 carbon of the thiazole ring); Mass (m/z):
597 (M+); Anal. Calcd for C30H17ClFN5O4S: C, 60.26; H,
2.87; N, 11.71. Found: C, 60.22; H, 2.85; N, 11.66.
1
(C=C), 1257 (C–O–C), 1109 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.57 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.76 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.33–8.05 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.56 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 115.0
(Ar–C), 115.6 (Ar–C), 116.1 (Ar–C), 118.8 (Ar–C), 124.8
(2C, Ar–C), 126.1 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C),
128.3 (Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.9 (Ar–C),
131.4 (Ar–C), 131.9 (Ar–C), 136.6 (Ar–C), 137.2 (Ar–C),
145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 149.6 (Ar–C),
152.7 (Ar–C), 152.9 (Ar–C), 160.6 (Ar–C), 162.9 (C=O
carbon of coumarin ring), 164.0 (Ar–C), 168.3 (C5 carbon
of the thiazole ring); Mass (m/z): 570 (M+); Anal. Calcd for
C30H17ClF2N4O2S: C, 63.11; H, 3.00; N, 9.81. Found:
C, 63.09; H, 2.99; N, 9.76.
3-(2-(3-(2-Chlorophenyl)-5-(2-chloroquinolin-3-yl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-iodo-2H-chromen-
2-one (9u) It was obtained by the reaction of the com-
pound (4e) with the compound (8a) as light-orange crystals
(EtOH).Yield 80%; m.p. 233–235 °C; Rf value 0.69; IR
(KBr) νmax 1717 (C=O), 1583 (C=N), 1533 (C=C), 1262
1
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(4-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-fluoro-2H-chro-
men-2-one (9s) It was obtained by the reaction of the
compound (4d) with the compound (8d) as brownish-
yellow crystals (EtOH). Yield 68%; m.p. 240–241 °C; Rf
value 0.72; IR (KBr) νmax 1716 (C=O), 1577 (C=N), 1533
(C–O–C), 1113 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.57 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.85 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.75 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.33–8.04 (m, 12H, Ar–H), 8.19 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.0 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 93.8 (Ar–C), 114.5 (Ar–C), 121.4
(Ar–C), 124.8 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 129.8 (Ar–C), 130.4 (Ar–C), 130.9
(Ar–C), 131.1 (Ar–C), 131.3 (Ar–C), 131.6 (Ar–C), 131.9
(Ar–C), 133.4 (Ar–C), 135.2 (Ar–C), 137.2 (Ar–C), 138.2
(2C, Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7
(Ar–C), 152.9 (2C, Ar–C), 162.9 (C=O carbon of coumarin
ring), 168.3 (C5 carbon of the thiazole ring); Mass (m/z): 694
(M+); Anal. Calcd for C30H17Cl2IN4O2S: C, 51.82; H, 2.46;
N, 8.06. Found: C, 51.80; H, 2.41; N, 8.05.
1
(C=C), 1263 (C–O–C), 1111 (C–S); H NMR (DMSO-d6,
400 MHz): δ = 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18
Hz, 1H, C5–H pyrazoline), 7.34–8.02 (m, 12H, Ar–H), 8.19
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 114.5 (Ar–C), 115.6
(Ar–C), 116.1 (Ar–C), 116.6 (2C, Ar–C), 124.8 (Ar–C),
126.1 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C),
128.5 (Ar–C), 130.4 (Ar–C), 130.5 (2C, Ar–C), 130.9
(Ar–C), 131.9 (Ar–C), 133.0 (Ar–C), 137.2 (Ar–C), 145.9
(Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 149.6 (Ar–C), 152.7
(Ar–C), 152.9 (Ar–C), 160.6 (Ar–C), 162.9 (C=O carbon
of coumarin ring), 166.2 (Ar–C), 168.3 (C5 carbon of the
thiazole ring); Mass (m/z): 570 (M+); Anal. Calcd for
C30H17ClF2N4O2S: C, 63.11; H, 3.00; N, 9.81. Found: C,
63.06; H, 2.95; N, 9.78.
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(2-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-iodo-2H-chromen-
2-one (9v) It was obtained by the reaction of the com-
pound (4e) with the compound (8b) as faint brownish-
yellow crystals (EtOH). Yield 75%; m.p. 241–243 °C; Rf
value 0.61; IR (KBr) νmax 1716 (C=O), 1578 (C=N), 1533
1
(C=C), 1257 (C–O–C), 1105 (C–S); H NMR (DMSO-d6,
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(4-nitrophenyl)-4,5-dihy-
dro-1H-pyrazol-1-yl)thiazol-4-yl)-6-fluoro-2H-chromen-2-
400 MHz): δ = 3.58 (d, J = 17 Hz, 1H, C4–H pyrazoline),
3.88 (d, J = 17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18

Med Chem Res
Hz, 1H, C5–H pyrazoline), 7.31–8.05 (m, 12H, Ar–H), 8.18
(s, 1H, C5–H thiazole), 8.55 (s, 1H, C4–H coumarin); 13C
NMR (DMSO-d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline
ring), 56.4 (C5 of the pyrazoline ring), 93.8 (Ar–C), 114.5
(Ar–C), 116.6 (Ar–C), 119.2 (Ar–C), 121.4 (Ar–C), 124.8
(Ar–C), 125.4 (Ar–C), 127.6 (Ar–C), 128.0 (Ar–C), 128.3
(Ar–C), 128.5 (Ar–C), 130.4 (Ar–C), 130.9 (Ar–C), 131.8
(Ar–C), 131.9 (Ar–C), 133.6 (Ar–C), 135.2 (Ar–C), 137.2
(Ar–C), 138.2 (Ar–C), 145.9 (Ar–C), 146.4 (Ar–C), 147.1
(Ar–C), 152.7 (Ar–C), 152.9 (2C, Ar–C), 160.6 (Ar–C),
162.9 (C=O carbon of coumarin ring), 168.3 (C5 carbon of
the thiazole ring); Anal. Calcd for C30H17ClFIN4O2S: C,
53.08; H, 2.52; N, 8.25. Found: C, 53.02; H, 2.48; N, 8.23.
(Ar–C), 135.2 (Ar–C), 137.2 (Ar–C), 138.2 (Ar–C), 145.9
(Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7 (Ar–C), 152.9
(2C, Ar–C), 162.9 (C=O carbon of coumarin ring), 166.2
(Ar–C), 168.3 (C5 carbon of the thiazole ring); Anal. Calcd
for C30H17ClFIN4O2S: C, 53.08; H, 2.52; N, 8.25. Found:
C, 53.00; H, 2.51; N, 8.23.
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(4-nitrophenyl)-4,5-dihy-
dro-1H-pyrazol-1-yl)thiazol-4-yl)-6-iodo-2H-chromen-2-
one (9y) It was obtained by the reaction of the compound
(4e) with the compound (8e) as light reddish-yellow crystals
(EtOH). Yield 68%; m.p. 251–253 °C; Rf value 0.73; IR
(KBr) νmax 1722 (C=O), 1585 (C=N), 1533 (C=C), 1266
1
(C–O–C), 1115 (C–S); H NMR (DMSO-d6, 400 MHz): δ
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(3-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-iodo-2H-chromen-
2-one (9w) It was obtained by the reaction of the com-
pound (4e) with the compound (8c) as yellow crystals
(EtOH). Yield 70%; m.p. 215–217 °C; Rf value 0.74; IR
(KBr) νmax 1719 (C=O), 1575 (C=N), 1534 (C=C), 1260
= 3.55 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.88 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.30–8.05 (m, 12H, Ar–H), 8.19 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 93.8 (Ar–C), 114.5 (Ar–C), 121.4
(Ar–C), 124.8 (Ar–C), 127.6 (Ar–C), 128.0 (3C, Ar–C),
128.3 (Ar–C), 128.5 (Ar–C), 128.7 (2C, Ar–C), 130.4
(Ar–C), 130.9 (Ar–C), 131.2 (Ar–C), 131.9 (Ar–C), 137.2
(Ar–C), 138.2 (Ar–C), 143.5 (A–-C), 145.9 (Ar–C), 146.4
(Ar–C), 147.1 (Ar–C), 151.2 (Ar–C), 152.7 (Ar–C), 152.9
(2C, Ar–C), 162.9 (C=O carbon of coumarin ring), 168.3
(C5 carbon of the thiazole ring); Mass (m/z): 705 (M+);
Anal. Calcd for C30H17ClIN5O4S: C, 51.04; H, 2.43; N,
9.92. Found: C, 51.01; H, 2.39; N, 9.92.
1
(C–O–C), 1110 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.55 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.86 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.30–8.04 (m, 12H, Ar–H), 8.20 (s, 1H, C5–H
thiazole), 8.54 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 93.8 (Ar–C), 114.5 (Ar–C), 115.0
(Ar–C), 118.8 (Ar–C), 121.4 (Ar–C), 124.8 (2C, Ar–C),
127.6 (Ar–C), 128.0 (Ar–C), 128.3 (Ar–C), 128.5 (Ar–C),
130.4 (Ar–C), 130.9 (Ar–C), 131.4 (Ar–C), 131.9 (Ar–C),
135.2 (Ar–C), 136.6 (Ar–C), 137.2 (Ar–C), 138.2 (Ar–C),
145.9 (Ar–C), 146.4 (Ar–C), 147.1 (Ar–C), 152.7 (Ar–C),
152.9 (2C, Ar–C), 162.9 (C=O carbon of coumarin ring),
164.0 (Ar–C), 168.3 (C5 carbon of the thiazole ring); Anal.
Calcd for C30H17ClFIN4O2S: C, 53.08; H, 2.52; N, 8.25.
Found: C, 53.01; H, 2.49; N, 8.22.
Antimicrobial activity
The targeted compounds (9a–9y) were tested for their
in vitro antimicrobial activity by the serial plate dilution
method (Cruickshank et al. 1975; Arthington-Skaggs et al.
2000) against five Gram-positive bacteria, namely, Sta-
phylococcus aureus (ATCC 25923), Enterococcus faecalis
(ATCC 29212), Staphylococcus epidermidis (ATCC
12228), Bacillus subtilis (ATCC 6633), and Bacillus cereus
(ATCC 9946); five Gram-negative bacteria, namely,
Escherichia coli (ATCC 25922), Pseudomonas aeruginosa
(ATCC 27853), Klebsiella pneumoniae (ATCC 700603),
Bordetella bronchiseptica (ATCC 4617) and Proteus vul-
garis (ATCC 9920); and five fungi, namely, Candida
albicans (ATCC 2091), Aspergillus niger (MTCC 281),
Aspergillus flavus (MTCC 277), Monascus purpureous
(MTCC 369), and Penicillium citrinum (NCIM 768). The
microorganisms were available at the Department of
Microbiology, Majeedia Hospital, New Delhi, India. The
Department of Microbiology of Majeedia Hospital obtained
some of these microorganisms from the Institute of Geno-
mics and Integrative Biology, New Delhi, India. Nutrient
agar medium and Sabouraud dextrose medium were used
3-(2-(5-(2-Chloroquinolin-3-yl)-3-(4-fluorophenyl)-4,5-
dihydro-1H-pyrazol-1-yl)thiazol-4-yl)-6-iodo-2H-chromen-
2-one (9x) It was obtained by the reaction of the com-
pound (4e) with the compound (8d) as orange crystals
(EtOH). Yield 77%; m.p. 236–238 °C; Rf value 0.66; IR
(KBr) νmax 1717 (C=O), 1581 (C=N), 1534 (C=C), 1255
1
(C–O–C), 1114 (C–S); H NMR (DMSO-d6, 400 MHz): δ
= 3.55 (d, J = 17 Hz, 1H, C4–H pyrazoline), 3.85 (d, J =
17 Hz, 1H, C4–H pyrazoline), 5.77 (d, J = 18 Hz, 1H, C5–H
pyrazoline), 7.30–8.05 (m, 12H, Ar–H), 8.19 (s, 1H, C5–H
thiazole), 8.55 (s, 1H, C4–H coumarin); 13C NMR (DMSO-
d6, 100 MHz): δ = 40.5 (C4 of the pyrazoline ring), 56.4 (C5
of the pyrazoline ring), 93.8 (Ar–C), 114.5 (Ar–C), 116.6
(2C, Ar–C), 121.4 (Ar–C), 124.8 (Ar–C), 127.6 (Ar–C),
128.0 (Ar–C), 128.3 (Ar–C), 128.5 (Ar–C), 130.4 (Ar–C),
130.5 (2C, Ar–C), 130.9 (Ar–C), 131.9 (Ar–C), 133.0

Med Chem Res
for antibacterial activity and antifungal activity, respec-
tively. The compounds were tested at concentrations of 200,
150, 100, 75, 50, 25, and 12.5 μg/mL. The reference or
standard antibiotics, ofloxacin, and ketoconazole were used
at 50, 25, and 12.5 μg/mL concentrations for antibacterial
activity and antifungal activity, respectively. Sterile dime-
thyl sulfoxide (DMSO) was used for the preparation of
desired concentrations of the synthesized compounds and
standard antibiotics. Sterile DMSO without the synthesized
compounds and standard antibiotics served as a control
group. The minimum inhibitory concentrations (MICs)
values of the synthesized compounds, ofloxacin, and keto-
conazole were also determined. The MIC (MIC) has been
defined as the lowest concentration of a compound that
inhibited visible growth of microorganisms on the plate.
The compounds (4a–4e) (Scheme 1) (Gali et al. 2015;
Siddiqui et al. 2009; Gursoy and Karali 2003; Aggarwal
et al. 2013; Jayashree et al. 2005; Venugopala and
Jayashree 2003; Chopra et al. 2006; Desai et al. 2013b), the
compound 5 (Scheme 2) (Desai et al. 2013a; Kumar et al.
2010), the compounds 7a–7e (Scheme 2) (Desai et al.
2013a; Kumar et al. 2010), and the compounds (8a–8e)
(Scheme 2) (Desai et al. 2013a) were prepared according to
the methods provided in the literature. The appropriate
compounds (4a–4e) and compounds (8a–8e) were reacted
in ethanol to provide the targeted compounds (9a–9y)
(Scheme 3). These targeted compounds were characterized
by their different melting points with respect to their
respective starting materials, different Rf values in a parti-
cular solvent system, elemental analysis, and spectral data
1
(IR, H-NMR, 13C-NMR, and Mass).
The IR spectra of the targeted compounds (9a–9y)
showed characteristic IR peaks for C=O and C–O–C
groups of coumarin ring at 1713–1723 and 1005–1118 cm-
1, respectively. It also displayed characteristic IR peak of C–
Statistical analysis
All data (n = 6) are presented as mean standard error
mean (SEM). The data were analyzed by one-way analysis
of variance (ANOVA) with Dunnett’s Multiple Comparison
Test with respect to control group and standard group using
GraphPad Prism version 5.00 for Windows, GraphPad
Software, San Diego California USA, www.graphpad.com.
The results were considered significantly different at p <
0.05 as compared with control group as well as standard
drug groups.
1
S group of the thiazole ring at 1255–1266 cm-1. The H-
NMR spectra of the targeted compounds (9a–9y) exhibited
characteristic signals for the methylene protons (C4–H
protons) of pyrazoline ring. One proton of the methylene
group of pyrazoline ring appeared as doublet at δ 3.55–3.61
and other proton appeared as doublet at δ 3.83–3.89. The
C5–H proton of the pyrazoline ring appeared as doublet at δ
5.75–5.78. The 1H-NMR spectra also showed characteristic
signals as multiplets at δ 7.30–8.09 for aromatic protons; as
singlet at δ 8.17–8.20 for C5–H proton of the thiazole ring
and as singlet at δ 8.53–8.56 for the C4–H proton of the
coumarin ring. The 13C-NMR spectra also supported the
assigned number of carbon atoms. It showed characteristic
signal at δ 40–40.5 due to the methylene carbon (C4) of the
pyrazoline ring and at δ 56.4 due to the methine carbon (C5)
Results and discussion
Chemistry
The targeted compounds (9a–9y) were prepared according
to the methods as depicted in Schemes 1–3.
Scheme 1 General procedure
for the synthesis of compounds
4a–4e

Med Chem Res
Scheme 2 General procedure
for the synthesis of compounds
8a–8e
Scheme 3 General procedure
for the synthesis of compounds
9a–9e

Med Chem Res
of the pyrazoline ring. The signals at about δ 168 and at about
δ 162.9 also confirmed the C5 carbon of the thiazole ring and
C=O carbon of coumarin ring, respectively. The molecular
ion peak of the mass spectrum as well as the elemental ana-
lysis of the targeted compounds (9a–9y) were also in accor-
dance with the assigned chemical structures. These spectral
data of the targeted compounds (9a–9y) were also in accor-
dance with the reported literature (Vijesh et al. 2010; Gali et al.
2015; Aggarwal et al. 2013; Desai et al. 2013a).
bacteria, Gram-negative bacteria, and fungi obtained by the
serial plate dilution method is provided in Tables 1, 2, and
Table 3, respectively.
In the following discussion, the zone of inhibition pro-
duced by the MIC of standard drugs, ofloxacin and keto-
conazole, has been considered as 100% for comparing the
antibacterial activity and antifungal activity of the targeted
compounds (9a–9y), respectively.
The antibacterial activity of the targeted compounds
(9a–9y) against Gram-positive bacteria revealed that the
standard drug ofloxacin had MIC values of 25 μg/mL
against S. aureus, E. faecalis, and S. epidermidis. It also had
a MIC value of 12.5 μg/mL against B. subtilis, and B.
cereus. The compound 9s (R=F, R1 = 4-F), exhibited the
Antimicrobial activity
The antimicrobial activity data of the targeted compounds
(9a–9y) at different concentrations against Gram-positive
Table 1 Antibacterial activity data of the targeted compounds (9a–9y) against Gram-positive bacteria
Compounds
Zone of inhibition in mm and MIC (minimum inhibitory concentration) in μg/mL
S. aureus
E. faecalis
S. epidermidis
B. subtilis
B. cereus
9a
11.48 0.25a (75)
16.62 0.50a (50)
19.47 0.48a (50)
18.21 0.34a (75)
10.40 0.46a (75)
13.14 0.29a (50)
21.63 0.27a (75)
23.13 0.44a (75)
11.85 0.35a (75)
14.20 0.30b (50)
16.02 0.39a (50)
17.95 0.18a (50)
17.19 0.38a (75)
23.40 0.46b (75)
15.83 0.45a (50)
22.06 0.35a (75)
25.89 0.32b (50)
26.11 0.38a (50)
27.52 0.38b (50)
20.27 0.30a (75)
5.64 0.28a (75)
8.96 0.44a (75)
15.02 0.32a (75)
21.61 0.37a (75)
14.58 0.60a (50)
27.81 0.46a (25)
0.0 0.0
13.23 0.37a (75)
17.73 0.29a (75)
19.03 0.17a (50)
18.88 0.30a (50)
12.74 0.40a (75)
14.52 0.51a (50)
20.34 0.44a (75)
22.32 0.31a (75)
13.62 0.29a (50)
14.61 0.36a (75)
16.23 0.18a (75)
18.49 0.28a (50)
17.99 0.41a (75)
22.82 0.39a (50)
15.53 0.33a (50)
22.01 0.34a (75)
23.25 0.41a (50)
25.07 0.40a (50)
25.94 0.42a (50)
19.22 0.33a (75)
12.02 0.18c (75)
12.55 0.30a (75)
15.14 0.17a (75)
19.98 0.27a (75)
15.09 0.29a (50)
31.03 0.46a (25)
0.0 0.0
13.17 0.51a (50)
18.33 0.28a (75)
20.93 0.34a (50)
20.33 0.38a (50)
12.68 0.56a (50)
16.48 0.41a (75)
22.92 0.29a (75)
26.18 0.28a (50)
15.29 0.34a (50)
16.53 0.28b (50)
18.04 0.32a (75)
20.22 0.41a (50)
18.83 0.22a (50)
26.21 0.31a (75)
17.57 0.39a (75)
23.57 0.42c (50)
26.25 0.28a (50)
27.34 0.38a (50)
29.43 0.28a (50)
21.04 0.41a (50)
10.03 0.25a (75)
10.12 0.44a (75)
17.48 0.37c (50)
21.49 0.36a (75)
17.02 0.44c (75)
30.03 0.45a (25)
0.0 0.0
11.55 0.33a (50)
16.80 0.39a (50)
18.44 0.44a (75)
18.44 0.32a (50)
9.32 0.45a (75)
13.28 0.40a (50)
19.15 0.38a (50)
23.03 0.44a (50)
13.23 0.33b (50)
13.89 0.29a (75)
16.55 0.26a (75)
18.07 0.31a (75)
16.91 0.40a (50)
23.15 0.34a (75)
16.33 0.31a (75)
21.96 0.36a (75)
23.60 0.34a (50)
24.25 0.32a (50)
27.69 0.49a (50)
18.72 0.46a (50)
5.09 0.43a (75)
9.20 0.26a (50)
16.08 0.46a (25)
18.83 0.28a (50)
15.80 0.48a (50)
34.73 0.45a (12.5)
0.0 0.0
15.50 0.31a (75)
21.25 045a (75)
22.90 0.13a (50)
22.22 0.36a (75)
15.48 0.26a (50)
18.80 0.23a (75)
25.49 0.24a (75)
26.16 0.45a (25)
18.65 0.35a (75)
19.80 0.33a (50)
20.89 0.13a (50)
22.11 0.30a (50)
21.89 0.13c (75)
26.94 0.34a (50)
20.83 0.26a (75)
25.80 0.37a (75)
27.50 0.35a (50)
28.47 0.33a (50)
29.33 0.39a (50)
23.47 0.44a (75)
10.24 0.43a (75)
14.03 0.31a (50)
20.28 0.27a (75)
23.73 0.43a (75)
20.20 0.39a (75)
32.08 0.30a (12.5)
0.0 0.0
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
9r
9s
9t
9u
9v
9w
9x
9y
Ofloxacin
Control
The values in brackets represent the MIC in μg/mL of the corresponding compounds
a
p < 0.0001 as compared to control and/or standard
b
p < 0.0001 as compared to control and p < 0.05 as compared to standard
c
p < 0.0001 as compared to control and p < 0.001 as compared to standard
d
p < 0.0001 as compared to control and p > 0.05 as compared to standard

Med Chem Res
Table 2 Antibacterial activity data of the targeted compounds (9a–9y) against Gram-negative bacteria
Compounds
Zone of inhibition in mm and MIC (minimum inhibitory concentration) in μg/mL
E. coli
P. aeruginosa
K. pneumonia
B. bronchiseptica
P. vulgaris
9a
8.30 0.45a (75)
18.26 0.50b (50)
18.23 0.47b (75)
18.33 0.38b (75)
18.22 0.33b (50)
13.65 0.44b (75)
23.83 0.39b (75)
18.00 0.40b (50)
25.25 0.47b (50)
17.70 0.51c (75)
10.77 0.27a (50)
22.33 0.38b (50)
15.35 0.28b (50)
23.59 0.33b (50)
15.21 0.43a (75)
14.49 0.31b (50)
27.50 0.33b (50)
26.67 0.31b (50)
28.71 0.30b (50)
16.23 0.31a (75)
10.05 0.25a (75)
20.49 0.33b (50)
15.91 0.31a (50)
21.00 0.47b (50)
15.73 0.18b (75)
31.61 0.41b (12.5)
0.0 0.0
10.70 0.41a (75)
22.51 0.34b (75)
22.13 0.38b (75)
23.25 0.29b (50)
21.70 0.27b (75)
15.29 0.46b (50)
26.60 0.41b (50)
21.04 0.40b (50)
27.25 0.34b (50)
20.16 0.44b (75)
13.11 0.35b (75)
23.79 0.42b (75)
16.80 0.38b (75)
26.18 0.27c (50)
16.19 0.30b (50)
15.98 0.38b (50)
30.19 0.32b (50)
29.0 0.41b (50)
30.28 0.41b (50)
18.44 0.37b (75)
12.76 0.49b (50)
23.67 0.30b (50)
18.20 0.29c (50)
23.76 0.43b (75)
16.91 0.34a (75)
34.23 0.14b (12.5)
0.0 0.0
12.26 0.41b (75)
30.16 0.27b (50)
13.51 0.45b (50)
22.32 0.32b (50)
23.69 0.47b (75)
22.09 0.31b (50)
28.78 0.42b (50)
18.49 0.51b (50)
23.41 0.32b (50)
24.66 0.42b (50)
21.18 0.45b (50)
18.51 0.31b (50)
12.72 0.38b (75)
22.44 0.26b (50)
21.47 0.28b (50)
9.23 0.41b (75)
23.62 0.36b (75)
31.30 0.32b (50)
25.29 0.38a (50)
11.45 0.33b (50)
14.44 0.41b (75)
22.07 0.41b (50)
10.77 0.25b (75)
18.51 0.35b (50)
18.05 0.41b (75)
31.55 01.9b (12.5)
0.0 0.0
19.73 0.41c (75)
27.56 0.32b (50)
15.07 0.37b (75)
20.13 0.13b (75)
25.68 0.42b (50)
13.05 0.41b (50)
20.01 0.34b (75)
21.73 0.28b (50)
26.03 0.40b (50)
13.44 0.55b (50)
18.58 0.42b (50)
26.84 0.18b (75)
19.95 0.37b (50)
22.15 0.42c (50)
18.00 0.31b (50)
16.99 0.31b (75)
25.08 0.29b (50)
26.26 0.46b (50)
25.97 0.32b (50)
12.50 0.33b (75)
21.69 0.42c (50)
29.84 0.31b (50)
12.76 0.50b (50)
12.22 0.44a (50)
26.33 0.29b (50)
34.80 0.24b (25)
0.0 0.0
14.80 0.27a (75)
15.57 0.27b (50)
23.41 0.38b (50)
23.61 0.39b (50)
13.67 0.29b (75)
27.01 0.27b (50)
23.83 0.35b (75)
26.11 0.36b (50)
20.42 0.35b (50)
13.73 0.36b (75)
9.39 0.41b (75)
12.68 0.33c (75)
13.41 0.35b (75)
21.43 0.39b (50)
15.05 0.29b (50)
15.03 0.41a (75)
24.93 0.44b (75)
24.55 0.38b (75)
29.74 0.28b (50)
23.70 0.43b (50)
18.59 0.48d (75)
25.95 0.41c (50)
22.33 0.39b (50)
17.09 0.40b (75)
18.13 0.30b (75)
32.08 0.31b (12.5)
0.0 0.0
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
9r
9s
9t
9u
9v
9w
9x
9y
Ofloxacin
Control
The values in brackets represent the MIC in μg/mL of the corresponding compounds
a
p < 0.0001 as compared to control and p < 0.05 as compared to standard
b
p < 0.0001 as compared to control and/or standard
c
p < 0.0001 as compared to control and p < 0.001 as compared to standard
d
p < 0.0001 as compared to control and p > 0.05 as compared to standard
highest activity of 98.95% (MIC = 50 μg/mL; p < 0.05),
83.59% (MIC = 50 μg/mL; p < 0.0001), 98% (MIC = 50 μg/
mL; p < 0.0001), 79.72% (MIC = 50 μg/mL; p < 0.0001),
and 91.42% (MIC = 50 μg/mL; p < 0.0001); the compound
9r (R=F, R1 = 3-F) showed activity of 93.88% (MIC = 50
μg/mL; p < 0.0001), 80.79% (MIC = 50 μg/mL; p < 0.0001),
91.04% (MIC = 50 μg/mL; p < 0.0001), 69.82% (MIC = 50
μg/mL; p < 0.0001), and 88.74% (MIC = 50 μg/mL; p <
0.0001); 9q (R=F, R1 = 2-F) displayed activity of 93.09%
(MIC = 50 μg/mL; p < 0.05), 74.92% (MIC = 50 μg/mL; p
< 0.0001), 87.41% (MIC = 50 μg/mL; p < 0.0001), 67.95%
(MIC = 50 μg/mL; p < 0.0001), and 85.72% (MIC = 50 μg/
mL; p < 0.0001) with respect to standard drug ofloxacin
against S. aureus, E. faecalis, S. epidermidis, B. subtilis, and
B. cereus, respectively.
The antibacterial activity of the targeted compounds
(9a–9y) against Gram-negative bacteria revealed that the
standard drug ofloxacin had MIC values of 12.5 μg/mL
against E. Coli, P. aeruginosa, K. pneumonia, and P. vul-
garis. It also had a MIC value of 25 μg/mL against B.
bronchiseptica. The compound 9s (R=F, R1 = 4-F) showed
higher activity of 90.82% (MIC = 50 μg/mL; p < 0.0001),
88.46% (MIC = 50 μg/mL; p < 0.0001), and 92.70% (MIC =
50 μg/mL; p < 0.0001) against E. coli, P. aeruginosa, and P.
vulgaris, respectively; and the compound 9r (R=F, R1 = 3-F)
displayed highest activity of 99.20% (MIC = 50 μg/mL;

Med Chem Res
Table 3 Antifungal activity data of the targeted compounds (9a–9y) against fungi
Compounds
Zone of inhibition in mm and MIC (minimum inhibitory concentration) in μg/mL
C. albicans
A. niger
A. flavus
M. purpureous
P. citrinum
9a
13.03 0.06a (150)
26.10 0.48c (75)
20.01 0.35c (75)
26.80 0.39c (75)
21.91 0.55c (75)
20.53 0.47c (75)
25.62 0.39c (75)
19.37 0.36c (100)
25.97 0.36c (75)
14.08 0.51a (100)
24.14 0.41c (100)
14.98 0.30c (150)
24.57 0.36c (75)
18.28 0.40c (100)
12.89 0.23c (50)
8.10 0.22c (150)
27.90 0.38c (50)
27.14 0.34c (50)
29.45 0.47c (50)
23.17 0.37c (100)
22.50 0.29c (75)
23.53 0.37c (75)
17.65 0.42c (50)
23.93 0.34c (100)
17.23 0.20c (100)
34.24 0.31c (12.5)
0.0 0.0
15.26 0.27b (75)
28.16 0.42c (75)
21.16 0.46c (75)
28.92 0.29a (100)
21.70 0.43c (100)
21.52 0.31b (75)
25.95 0.43c (75)
21.01 0.38c (75)
26.13 0.43c (75)
15.51 0.36c (75)
24.32 0.45c (75)
18.10 0.59d (100)
24.77 0.32c (75)
20.12 0.53c (75)
13.80 0.45c (50)
11.61 0.30b (100)
29.19 0.27b (50)
28.97 0.28a (50)
29.42 0.21c (50)
23.49 0.42c (75)
23.12 0.30c (75)
23.77 0.37c (75)
19.08 0.49c (100)
24.11 0.38c (75)
18.66 0.34c (75)
30.71 0.41c (12.5)
0.0 0.0
15.45 0.30c (50)
27.57 0.32c (75)
19.41 0.10c (150)
27.97 0.36c (75)
19.83 0.36c (100)
19.68 0.41c (75)
26.16 0.31a (100)
18.93 0.38b (75)
26.84 0.49a (100)
15.99 0.25c (75)
25.0 0.37c (100)
16.12 0.38c (100)
25.88 0.27b (75)
18.80 0.44c (75)
10.33 0.11d (100)
9.60 0.41a (150)
28.75 0.46b (50)
28.30 0.29a (50)
29.05 0.37b (50)
22.09 0.54c (75)
21.0 0.37c (100)
22.17 0.47c (75)
18.71 0.43b (100)
22.86 0.37c (75)
18.68 0.25c (100)
29.93 0.56c (25)
0.0 0.0
16.28 0.28c (75)
26.67 0.39c (100)
20.69 0.35c (75)
29.34 0.31c (100)
21.49 0.46c (75)
21.36 0.46c (75)
26.35 0.48c (75)
20.09 0.38c (75)
26.41 0.27c (75)
16.40 0.41a (75)
24.01 0.45c (100)
18.40 0.38c (75)
24.42 0.45c (75)
19.91 0.41c (75)
15.34 0.41c (150)
13.29 0.17c (75)
30.19 0.17c (50)
29.54 0.47c (50)
30.33 0.35c (50)
22.62 0.39c (75)
22.13 0.38c (75)
23.18 0.38c (75)
18.51 0.35b (100)
23.32 0.37c (75)
18.50 0.52c (75)
34.45 0.36c (12.5)
0.0 0.0
17.36 0.31c (75)
26.75 0.36b (100)
21.86 0.37c (75)
27.36 0.66a (100)
22.41 0.45c (100)
22.35 0.49c (100)
25.67 0.42c (100)
21.28 0.29c (75)
26.20 0.30c (100)
18.34 0.45c (75)
25.26 0.26c (75)
19.38 0.46c (75)
25.39 0.49c (100)
21.21 0.37c (75)
17.33 0.43c (100)
12.42 0.40c (100)
30.94 0.32c (50)
29.90 0.31a (50)
30.99 0.30c (50)
23.76 0.35c (75)
23.68 0.52c (75)
24.04 0.55c (75)
21.10 0.44c (75)
24.34 0.35c (100)
19.91 0.43c (50)
28.68 0.31c (25)
0.0 0.0
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
9r
9s
9t
9u
9v
9w
9x
9y
Ketoconazole
Control
The values in brackets represent the MIC in μg/mL of the corresponding compounds
a
p < 0.0001 as compared to control and p < 0.05 as compared to standard
b
p < 0.0001 as compared to control and p < 0.001 as compared to standard
c
p < 0.0001 as compared to control and/or standard
d
p < 0.0001 as compared to control and p > 0.05 as compared to standard
p < 0.0001) against K. pneumonia; and compound 9v (R =
I; R1 = 2-F) exhibited highest activity of 85.74% (MIC =
50 μg/mL; p < 0.0001) against B. bronchiseptica. Further,
the compound 9q (R=F, R1 = 2-F) and 9r (R=F, R1 = 3-F)
displayed activity of 86.99% (MIC = 50 μg/mL; p < 0.05)
and 84.37% (MIC = 50 μg/mL; p < 0.0001) against E. coli,
respectively. These compounds also exhibited activity of
88.19% (MIC = 50 μg/mL; p < 0.0001) and 84.72% (MIC
= 50 μg/mL; p < 0.0001) against P. aeruginosa, respec-
tively. The compound 9b (R = H, R1 = 2-F) and 9g (R =
Cl, R1 = 2-F) showed activity of 95.59% (MIC = 50 μg/mL;
p < 0.0001) and 91.22% (MIC = 50 μg/mL; p < 0.0001)
against K. pneumonia, respectively. The compound 9b (R
= H, R1 = 2-F) and 9l (R = Br, R1 = 2-F) showed activity
of 79.19% (MIC = 50 μg/mL; p < 0.0001) and 77.12%
(MIC = 75 μg/mL; p < 0.0001) against B. bronchiseptica,
respectively. The compound 9f (R = Cl, R1 = 2-Cl) and 9h
(R = Cl, R1 = 3-F) showed activity of 84.19% (MIC = 50
μg/mL; p < 0.0001) and 81.39% (MIC = 50 μg/mL; p <
0.0001) against P. vulgaris, respectively.
The antifungal activity of the targeted compounds
(9a–9y) against fungi revealed that the standard drug
ketoconazole had MIC values of 12.5 μg/mL against C.
albicans, A. niger, and M. purpureous. It also had MIC
value of 25 μg/mL against A. flavus and P. citrinum. The
compound 9s (R=F, R1 = 4-F), exhibited the highest
activity of 98.95% (MIC = 50 μg/mL; p < 0.0001), 83.59%
(MIC = 50 μg/mL; p < 0.0001), 98% (MIC = 50 μg/mL;

Med Chem Res
Conflict of interest The authors declare that they have no competing
interests.
p < 0.001), 79.72% (MIC = 50 μg/mL; p < 0.0001), and
91.42% (MIC = 50 μg/mL; p < 0.0001); the compound 9r
(R=F, R1 = 3-F) showed activity of 79.26% (MIC = 50 μg/
mL; p < 0.0001), 94.33% (MIC = 50 μg/mL; p < 0.05),
94.55% (MIC = 50 μg/mL; p < 0.05), 85.74% (MIC = 50
μg/mL; p < 0.0001), and 104.25% (MIC = 50 μg/mL; p <
0.05); and the compound 9q (R=F, R1 = 2-F) displayed
activity of 81.48% (MIC = 50 μg/mL; p < 0.0001), 95.05%
(MIC = 50 μg/mL; p < 0.001), 96.05% (MIC = 50 μg/mL;
p < 0.001), 87.63% (MIC = 50 μg/mL; p < 0.0001), and
107.88% (MIC = 50 μg/mL; p < 0.0001) with respect to
standard drug ketoconazole against C. albicans, A. niger, A.
flavus, M. purpureous, and P. citrinum, respectively.
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Med Chem Res
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