3-Aryl/Heteryl-5-Phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-ones: Synthesis, Characterization, and Antimicrobial Investigation

Article abstract of DOI:10.1134/S106816202004007X

Abstract: Discovery towards the potent antimicrobial agents is indispensable for the treatment of infections caused by resistant microbes. Thus, we prepared a novel series of 3-substituted 5-phenylindeno-thiazolopyrimidinone derivatives following conventional method. All the molecules were investigated for their in vitro antimicrobial potency against different bacteria and fungi, and the results were compared with streptomycin and clotrimazole standard drugs, respectively. Among the twelve analogs, 4-methoxyphenyl-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one showed equipotent activity against a bacterium, Staphylococcus aureus (minimum inhibitory concentration 25 μg/mL and zone of inhibition 22 mm), and a fungus, Aspergillus niger (zone of inhibition 20 mm). The rest of the thiazolo[3,2-a]pyrimidin-6(5H)-one derivatives exhibited week to reasonable activities against the tested bacterial and fungal strains.

Full text of DOI:10.1134/S106816202004007X

ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2020, Vol. 46, No. 4, pp. 612–619. © Pleiades Publishing, Ltd., 2020.
3
-Aryl/Heteryl-5-Phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-
6
(5H)-ones: Synthesis, Characterization, and Antimicrobial
Investigation
a
b
b, 1
c
d, e
a
G. Rajitha , C. G. Arya , B. Janardhan , S. V. Laxmi , G. Ramesh , and U. Sujana Kumari
a
Department of Chemistry, Gayatri Vidya Parishad College of Engineering (A), Andhra Pradesh, 530048 India
b
Department of Chemistry, National Institute of Technology Calicut, Kerala, 673601 India
Department of Chemistry, Palamuru University, Mahabubnagar, Telangana State, 509001 India
Department of Chemistry, National Institute of Technology Warangal, Warangal, Telangana State, 506004 India
c
d
e
Division of Environmental Monitoring and Exposure Assessment (Air) Laboratory, ICMR-NIREH,
Bhopal, Madhya Pradesh, 462030 India
Received July 29, 2019; revised September 13, 2019; accepted October 29, 2019
Abstract—Discovery towards the potent antimicrobial agents is indispensable for the treatment of infections
caused by resistant microbes. Thus, we prepared a novel series of 3-substituted 5-phenylindeno-thiazo-
lopyrimidinone derivatives following conventional method. All the molecules were investigated for their
in vitro antimicrobial potency against different bacteria and fungi, and the results were compared with
streptomycin and clotrimazole standard drugs, respectively. Among the twelve analogs, 4-methoxyphe-
nyl-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one showed equipotent activity against a
bacterium, Staphylococcus aureus (minimum inhibitory concentration 25 μg/mL and zone of inhibition
2
2 mm), and a fungus, Aspergillus niger (zone of inhibition 20 mm). The rest of the thiazolo[3,2-
a]pyrimidin-6(5H)-one derivatives exhibited week to reasonable activities against the tested bacterial
and fungal strains.
Keywords: antimicrobial activity, 3-(bromoacetyl)coumarin, 1,3-indandione, phenacyl bromide, thiazolopy-
rimidinone
DOI: 10.1134/S106816202004007X
INTRODUCTION
applications, such as antimicrobial [7–9], antibiofilm
10, 11], anticancer [12, 13], antiviral [14], anti-
[
Antibacterial resistance is growing tremendously
throughout the world due to the misuse and overuse of
the antibiotics. Thus, it is a serious threat for the suc-
cessful treatment of the infectious diseases and
becomes a foremost clinical and public health prob-
lem. According to the World Health Organization
inflammatory [15–18], antitubercular [8], anti-
tumoural [19], antimalarial [20], anti-HIV [20, 21],
antioxidant [7, 22], and calcium channel blocking [23]
activities. They are also reported as inhibitors of ace-
tylcholinesterase (AchE) [24, 25], CDC25B phospha-
tase [26], and xanthine oxidase [27] enzymes, and
Bcl-2 family proteins [28]. These are also considered
as potential purine antagonists [29, 30]. The structures
of some of the thiazolopyrimidine derivatives and their
biological properties are specified in Fig. 1 [31].
(
WHO), approximately 700000 deaths occur annually
due to drug-resistant pathogens, and this number is
likely to reach 10 million by 2050 if the existing trend
continues [1–3]. Hence, it is essential to develop new
classes of highly effective antimicrobial agents with no
side effects to fight against pathogenic microorgan-
isms that developed resistance to the antibiotics used
in the current regimen [4–6].
In view of the remarkable pharmacological proper-
ties of thiazolo[3,2-a]pyrimidines, numerous meth-
ods have been accounted for their synthesis. One of
the simplest method is the cyclization of dihydropy-
rimidine-thiones (Biginelli product) with halogen-
Thiazolopyrimidine derivatives have received a sig-
nificant interest from the medicinal and synthetic
chemists because of their extensive pharmacological
(
bromo- or chloro-) containing electrophiles like
2
-bromo-ketones [32], chloroacetyl chloride [26],
1
chloroacetic acid [12–14], 1,2-dichloroethane [33],
and methyl chloroacetate [34] to yield various C2–N3
Corresponding author: phone: 0091-0891-2535788; e-mail:
janardhan@nitc.ac.in.
612

3-ARYL/HETERYL-5-PHENYLINDENO[1,2-d]THIAZOLO[3,2-a]PYRIMIDIN-6(5H)-ONES
613
F
O N
MeOOC
O
N
MeO
2
CH3
O
N
EtOOC
Ph
N
F
N
N
S
S
H C
S
H C
3
3
N
H C
N
3
Calcium channel blocking activity
Ritanserin
serotonin receptor antagonist)
Anti-inflammatory activity
(
Fig. 1. Some of the biologically active thiazolo[3,2-a]pyrimidine derivatives.
linked various thiazolo[3,2-a]pyrimidines. Motivated thiazolo[3,2-a]pyrimidines starting from 1,3-indandi-
by the aforementioned findings, and in continuation
of our investigation towards the development of highly
potent antimicrobial agents [35–37], herein we report
the synthesis, characterization, and in vitro antimicrobial
investigation of fused thiazolopyrimidine derivatives.
one. Biginelli product, 4-phenyl-2-thioxo-3,4-dihy-
dro-1H-indeno[1,2-d]pyrimidin-5(2H)-one (III) was
prepared via a three-component condensation reac-
tion of 1,3-indandione, benzaldehyde, and thiourea
utilizing a catalyst, poly(4-vinylpyridinium)hydrogen
sulfate [P(4-VPH)HSO ]. The reaction mixture was
subjected to heat at 120°C under neat conditions. The
4
RESULTS AND DISCUSSION
In our previous report [7], we synthesized several intermediate (III) was obtained in 94% yield in short
fused thiazolo[3,2-a]pyrimidines starting from reaction time (15 min). The expected products (IVa–l),
1
-tetralone and investigated their in vitro antibacterial
were obtained in 80–90% yields via the cyclization of
an intermediate (III) with a variety of bromine derived
electrophiles, such as phenacyl bromides and 3-(bro-
moacetyl)coumarins (IIa–e) under conventional reflux-
ing in acetic acid (Scheme 2). 3-(Bromoacetyl)coumarin
derivatives (IIa–e) were prepared following the earlier
potency against different bacteria. We observed that
the analogs bearing aryl substitutions on the thiazole
ring had nearly 1.3 fold potency against a gram-nega-
tive bacteria Pseudomonas aeruginosa when compared
with an antibiotic penicillin. Keeping this in mind and
to examine the effect of fused ring on antimicrobial
activity, we designed to synthesize a small library of literature procedure (Scheme 1) [38].
R3
R1
R3
R1
O
O
R3
R1
O
O
O
O
R2
CHO
OH
R2
R2
Br
i
CH3
ii
CH3
+
O
(
O
EtO
Ia−e)
(IIa−e)
a: R = R = R = H
b: R = OCH , R = R = H
1 3 2 3
1
2
3
c: R = OCH , R = Br, R = H
d: R = R = NO , R = H
1 2 2 3
1
3
2
3
e: R = H, R −R = C H
4
1
2
3
6
Reagents and conditions: (i) Ethanol, piperidine (cat.), rt 1–2 h (for Ia–d); ethanol, piperidine (cat.), reflux,
2
h (for Ie); (ii) bromine, dry chloroform, 60°C, 2 h.
Scheme 1. Synthesis of 3-(2-bromoacetyl)-2H-chromen-2-ones and 2-(2-bromoacetyl)-
3
H-benzo[f]chromen-3-one (IIa–e).
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 4 2020

6
14
RAJITHA et al.
Ph
Ph
N
O
O
R
S
O
O
H N
i
NH
ii
N
2
+
Ph CHO +
H N
2
S
N
H
S
(
III)
(IVa−l)
a: R = C H
g: R = 4-PhC H
6 4
6
5
b: R = 4-ClC H
h: R = Coumarin-3-yl
i: R = 8-Methoxy coumarin-3-yl
6
4
c: R = 4-BrC H
6
4
d: R = 4-NO C H
j: R = 5-Bromo-8-methoxy coumarin-3-yl
k: R = 5,8-Dinitro coumarin-3-yl
2
6
4
e: R = 4-CH C H
3
6
4
f: R = 4-OCH C H l: R = 3H-Benzo[f]chromen-3-one-2-yl
3
6
4
Reagents and conditions: (i) Poly(4-vinylpyridinium)hydrogen sulfate, solvent-free, 120°C, 15 min;
ii) phenacyl bromides (for IVa−g), 3-(2-bromoacetyl)-2H-chromen-2-ones (for IVh−k),
(
2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one (for IVl), acetic acid, 120°C, 2−5 h.
Scheme 2. Synthesis of 5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one derivatives.
Formation of the target compounds (IVa–l) from phenyl (IVe), and biphenyl (IVg) groups did not
the intermediate dihydropyrimidine-thione (III) was improve the antibacterial activity against S. aureus.
1
13
confirmed by FT-IR, H, C NMR, mass spectrome- Introducing coumarinyl groups (IVh–l) into thiazole
try and elemental analyses data. The disappearance of ring also did not enhance the activity. Weak activity
–
1
was observed for all the synthesized molecules against
S. pyogene and K. pneumonia bacterial strains compar-
ing with the reference drug.
–
NH bands at 3406 and 3280 cm of the dihydropy-
rimidin-thione (III) and the existence of imine
–
1
‒
C=N– band at 1604–1647 cm in the FT-IR spec-
tra confirm the product formation. In case of com-
Antifungal activity was assayed against Candida
glabrata, Candida albicans, Aspergillus parasiticus, and
Aspergillus niger fungal strains. Clotrimazole was used
as a reference drug. Activity results reveal that the
maximum ZOI (20 mm) has observed in the case of
compound (IVf) against A. niger. Compounds (IVa),
–1
pounds (IVh–l), a strong band at 1732–1738 cm sig-
nifies the existence of pyranone (–O–C=O) group.
The disappearance of singlets at 9.78 and 11.68 ppm
1
from the H NMR spectra and a signal at 174.32 ppm
13
from C NMR spectra of the starting material, as well
as the presence of a peak –of –C=N (imine carbon) at
(
IVc), (IVf), and (IVk) showed good activity (ZOI 11–
1
57.47–158.64 ppm indicate the construction of the
2
0 mm) against all the tested fungal strains (Table 2,
product. Elemental analyses and mass spectral data
further strengthened the formation of products.
Fig. 2). Moderate-to-weak activity was observed in the
case of the rest of the molecules.
Antibacterial activity of all the synthesized mole-
cules (IVa–l) was measured against gram-positive
Streptococcus pyogene and Staphylococcus aureus and
gram-negative Klebsiella pneumonia and Pseudomonas
aeruginosa bacterial strains. Streptomycin was used as
CONCLUSION
3-Aryl/Heteryl substituted 5-phenylindeno-thi-
a standard antibacterial drug. Almost all the com- azolopyrimidinone derivatives (IVa–l) were prepared
pounds (except for compound (IVa)) showed moder- with promising yields under conventional method. All
ate activity against a gram-negative bacterium P. aeru- the synthesized molecules (IVa–l) were investigated
ginosa in terms of ZOI (14–18 mm) and MIC (50– for their antimicrobial potency against different
100 μg/mL) values comparing with a standard antibi- microbes. The activity data revealed that the com-
otic drug streptomycin. Compound (IVa) showed pound containing the 4-methoxyphenyl group on the
weak activity against P. aeruginosa. But the compound thiazole ring (IVf) has broad-spectrum antibacterial
derived from 4-methoxyphenacyl bromide (IVf) and antifungal activities against all the microbes used
showed equipotent activity against S. aureus (gram- for the investigation. Compounds (IVa), (IVc), and
positive) in terms of ZOI (22 mm) MIC (25 μg/mL) (IVk) also showed good antifungal activity. Taking
values (Table 1, Fig. 2). Replacing the 4-methoxyphe- compound (IVf) as a lead, further modifications by
nyl group of thiazole ring with 4-chlorophenyl (IVb), substituents on the pyrimidine ring are under investi-
4-bromophenyl (IVc), 4-nitrophenyl (IVd), 4-methyl- gation in our laboratory.
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3-ARYL/HETERYL-5-PHENYLINDENO[1,2-d]THIAZOLO[3,2-a]PYRIMIDIN-6(5H)-ONES
615
Table 1. Antibacterial activity results of substituted indeno-thiazolo-pyrimidinone derivatives (IVa–l)
Antibacterial activity
Analog
S. pyogenes
S. aureus
MIC
K. pneumoniae
ZOI MIC
200
P. aeruginosa
ZOI MIC
200
ZOI
MIC
ZOI
(
(
(
(
(
(
(
(
IVa)
IVb)
IVc)
IVd)
IVe)
IVf)
IVg)
IVh)
8
8
8
8
8
14
8
12
8
8
16
8
200
200
200
200
200
100
200
100
200
200
50
16
11
8
13
14
22
8
8
8
8
16
8
50
100
200
100
100
25
200
200
200
200
50
8
8
8
8
200
200
200
200
100
200
200
200
200
200
200
50
18
15
16
18
16
14
16
17
18
16
17
20
50
100
50
50
50
100
50
50
50
50
8
8
15
8
8
(
IVi)
IVj)
IVk)
8
8
8
8
(
(
(IVl)
200
12.5
200
25
50
12.5
Streptomycin
21
22
22
Zone of inhibition (mm) values were measured at 150 μg/mL for compounds (IVa–l) and 30 μg/mL for standard drug.
Table 2. Antifungal activity results of substituted indeno-thiazolo-pyrimidinone derivatives (IVa–l)
Antifungal activity (ZOI in mm)
Analog
Candida glabrata
Candida albicans
Aspergillus parasiticus
Aspergillus niger
(
(
(
(
(
(
(
(
IVa)
IVb)
IVc)
IVd)
IVe)
IVf)
IVg)
IVh)
19
12
16
8
14
13
8
8
14
8
17
8
18
8
8
11
8
8
8
8
15
8
16
8
16
8
12
14
8
8
12
8
14
10
20
16
8
11
8
10
20
8
10
12
10
16
10
20
(
IVi)
IVj)
IVk)
(
(
18
10
22
(
IVl)
Clotrimazole
24
Zone of inhibition (mm) values were measured at 150 μg/mL for compounds (IVa–l) and 30 μg/mL for standard drug.
EXPERIMENTAL
acetate as eluent was used for the purification of the
final molecules. Buchi (R-100) rotary evaporator was
used to remove the solvents. Stuart SMP30 melting
point apparatus was used to find out the melting point
of the compounds. Perkin-Elmer 100S IR spectro-
photometer was used to record the IR spectra (νmax,
All of the solvents and reagents used were obtained
commercially from Aldrich, SRL, and Qualigens
chemicals, and are used as is unless otherwise men-
tioned. Thin layer chromatography (silica gel 60F
254
pre-coated aluminum sheets obtained from Aldrich)
was used to examine the development of the reaction.
Column chromatography (silica-gel, 230–400 mesh
–1
cm ) in KBr. Bruker 400MHz spectrometer was used
1
to record the NMR spectra in DMSO-d at 400 ( H)
6
13
procured from Aldrich) with 80% hexanes and ethyl and 100 ( C) MHz; chemical shifts values are given in
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 4 2020

6
16
RAJITHA et al.
a)
2
5
0
(
2
S. aureus
15
S. pyogenes
P. aeruginosa
K. pneumoniae
1
0
5
0
IVa
IVc
IVe
IVg
IVi
IVk Streptomycin
IVj IVl
IVb
IVd
IVf
IVh
2
5
0
(b)
2
1
5
C. albicans
C. glabrata
A. niger
10
5
0
A. parasiticus
IVa
IVc
IVe
IVg
IVi
IVk Clotrimazole
IVb
IVd
IVf
IVh
IVj
IVl
Compounds
Fig. 2. Preliminary antibacterial (a) and antifungal (b) activities of 3-substituted-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimi-
din-6(5H)-ones (IVa–l).
ppm (parts per million). Jeol JMSD-300 spectrometer
and Carlo Erba EA1108 analytical unit were used to din-6(5H)-one (IVa). To the stirred intermediate com-
record mass spectra and elemental analysis data.
pound (III) (1 mmol, 292.35 mg) in glacial AcOH
4 mL) phenacyl bromide (1 mmol, 199.05 mg) was
3,5-Diphenylindeno[1,2-d]thiazolo[3,2-a]pyrimi-
(
4
-Phenyl-2-thioxo-3,4-dihydro-1H-indeno[1,2-
added. The temperature of the reaction mixture was
raised to 120°C and the mixture was stirred at that
same temperature for 3 h, then kept a side for 12 h.
Precipitate separated out was filtered and washed with
small amount of cold acetic acid. The crude material
obtained was subjected to column chromatography
using 20% ethyl acetate in hexanes to obtain the pure
product (IVa) as an orange solid (83%, 325.73 mg). mp
d]pyrimidin-5(2H)-one (III). To a mixture of 1,3-
indandione (10 mmol, 1.461 g), benzaldehyde
(
1
10 mmol, 1.02 mL), and thiourea (12 mmol, 0.913 g),
5 mg of P(4-VPH)HSO was added. The mixture was
4
heated at 120°C for 15 min under neat conditions.
Dichloromethane (50 mL) was added to the reaction
mixture and stirred at ambient temperature for addi-
tional 5 min, and the catalyst was filtered off. The
crude product was purified by crystallization using
2
(
(
61–263°C; IR: 1707 (C=O), 1600 (C=N), 1562
C=C). H NMR: 6.35 (s, 1H, H4pyrimidine), 6.63–6.65
m, 2H, Ar–H and H2thiazole), 7.10 (t, J = 7.2 Hz, 4H,
1
ethanol to obtain pure intermediate (III) as a red solid
2.748 g, 94%). mp 224–226°C; H NMR: 5.36 (s,
H, H4
1
(
1
), 7.25–7.39 (m, 8H, Ar-H), 7.86–7.91 Ar–H), 7.22–7.24 (m, 3H, Ar–H), 7.32 (d, J =
pyrimidine
(
m, 1H, Ar-H), 9.77 (bs, 1H, NH), 11.68 (bs, 1H, 7.2 Hz, 1H, Ar–H), 7.36–7.46 (m, 4H, Ar–H), 7.55
+
(
d, 3H, Ar–H, J = 7.6 Hz); MS (ESI, m/z): 393 [M +
NH); MS (ESI, m/z): 293 [M + H] ; Anal. calcd. for
+
C H N OS: C, 69.84; H, 4.14; N, 9.58. Found: C, H] ; Anal. calcd. for C H N OS: C, 76.51; H, 4.11;
1
7
12
2
25 16
2
6
9.67; H, 4.31; N, 9.41.
N, 7.14. Found: C, 76.40; H, 4.25; N, 7.33.
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3-ARYL/HETERYL-5-PHENYLINDENO[1,2-d]THIAZOLO[3,2-a]PYRIMIDIN-6(5H)-ONES
617
1
Compounds (IVb–l) were synthesized similarly as 1190 (C–O–C). H NMR: 3.79 (s, 3H, OCH ), 6.36
3
compound (IVa).
-(4-Chlorophenyl)-5-phenylindeno[1,2-d]thiazolo- 3H, J = 8.4 Hz, Ar–H), 7.12–7.17 (m, 6H, Ar–H),
3,2-a]pyrimidin-6(5H)-one (IVb). 4-Chlorophenacyl 7.25–7.46 (m, 4H, Ar–H); MS (ESI, m/z): 423 [M +
(
s, 1H, H4
), 6.69 (s, 1H, H2
), 6.93 (d,
thiazole
pyrimidine
3
[
+
bromide (1 mmol, 233.49 mg) was used as reagent. H] ; Anal. calcd. for C H N O S: C, 73.91; H, 4.29;
2
6
18
2
2
Orange solid (90%, 384.22 mg); mp 254–256°C; IR:
717 (C=O), 1605 (C=N), 1575 (C=C), 749 (C–Cl).
N, 6.63. Found: C, 73.79; H, 4.13; N, 6.51.
1
3
-([1,1'-Biphenyl]-4-yl)-5-phenylindeno[1,2-d]-
1
H NMR: 6.34 (s, 1H, H4pyrimidine), 6.68–6.71 (m, 2H,
Ar–H and H2 ), 7.11–7.15 (m, 7H, Ar–H), 7.26
thiazolo[3,2-a]pyrimidin-6(5H)-one (IVg). 4-Phenyl-
thiazole
phenacyl bromide (1 mmol, 275.14 mg) was used as
(
t, 3H, J = 8.4 Hz, Ar–H), 7.43 (t, 2H, J = 8.4 Hz,
reagent. Yellow solid (80%, 374.85 mg); mp 276–
+
1
Ar–H); MS (ESI, m/z): 427 [M + H] ; Anal. calcd.
for C H ClN OS: C, 70.33; H, 3.54; N, 6.56;
2
78°C; IR: 1711 (C=O), 1645 (C=N), 1571 (C=C). H
2
5
15
2
NMR: 6.45 (s, 1H, H4
), 6.72–6.74 (m, 2H,
pyrimidine
), 7.11 (t, 3H, J = 7.2 Hz, Ar–H),
Found: C, 70.15; H, 3.67; N, 6.39.
-(4-Bromophenyl)-5-phenylindeno[1,2-d]thiazolo- 7.31 (t, 5H, J = 8.4 Hz, Ar–H), 7.42–7.51 (m, 5H,
Ar–H and H2
thiazole
3
13
[
3,2-a]pyrimidin-6(5H)-one (IVc). 4-Bromophenacyl Ar–H), 7.67–7.73 (m, 4H, Ar–H); C NMR: 188.98,
bromide (1 mmol, 277.94 mg) was used as reagent. 157.84, 141.35, 141.12, 140.47, 139.01, 138.34, 133.98,
Orange solid (88%, 414.8 mg); mp 264–266°C; IR: 132.11, 130.41, 129.93, 129.05, 128.40, 128.18, 128.04,
1
714 (C=O), 1604 (C=N), 1576 (C=C), 616 (C–Br). 127.49, 126.79, 126.54, 125.96, 120.71, 119.35, 108.94,
1
+
H NMR: 6.34 (s, 1H, H4pyrimidine), 6.69–6.71 (m, 2H, 105.32, 58.99; MS (ESI, m/z): 469 [M + H] ; Anal.
Ar–H and H2
), 7.11–7.23 (m, 7H, Ar–H), 7.31 calcd. for C H N OS: C, 79.46; H, 4.30; N, 5.98.
thiazole
31 20
2
(
d, 1H, J = 7.2 Hz, Ar–H), 7.40 (t, 2H, J = 7.6 Hz, Found: C, 79.31; H, 4.47; N, 5.81.
Ar–H), 7.58 (d, 2H, J = 8.8 Hz, Ar–H); MS (ESI,
3
-(2-Oxo-2H-chromen-3-yl)-5-phenylindeno[1,2-
d]thiazolo[3,2-a]pyrimidin-6(5H)-one (IVh). 3-(2-
C, 63.70; H, 3.21; N, 5.94. Found: C, 63.57; H, 3.39; Bromoacetyl)-2H-chromen-2-one (1 mmol, 267.07 mg)
N, 5.80.
was used as reagent. Yellow solid (84%, 386.82 mg);
mp 238–240°C; IR: 1737 (C=O ) 1702 (C=O ),
+
m/z): 472 [M + H] ; Anal. calcd. for C H BrN OS:
2
5
15
2
3
-(4-Nitrophenyl)-5-phenylindeno[1,2-d]thiazolo-
3,2-a]pyrimidin-6(5H)-one (IVd). 4-Nitrophenacyl 1646 (C=N), 1581 (C=C); H NMR: 5.76 (s, 1H,
bromide (1 mmol, 244.04 mg) was used as reagent. H4 ), 6.82 (s, 1H), 6.91 (t, 3H, J = 8.0 Hz), 7.13
lactone
1
indanone
[
pyrimidine
Yellow solid (81%, 354.35 mg); mp 271–273°C; IR: (d, 2H, J = 8.0 Hz), 7.25 (d, 1H, J = 6.8 Hz), 7.29 (s,
1
715 (C=O), 1604 (C=N), 1574 (C=C), 1548, 1384 1H, H2
), 7.36 (t, 2H, J = 6.4 Hz, Ar–H), 7.51 (d,
thiazole
1
(
(
NO ). H NMR: 6.39 (s, 1H, H4
), 6.69–6.71 2H, J = 8.4 Hz, Ar–H), 7.61 (d, 1H, J = 7.6 Hz, Ar–
pyrimidine
2
m, 2H, Ar–H and H2
.22–7.34 (m, 3H, Ar–H), 7.40 (t, 2H, J = 6.8 Hz, H4
), 7.07–7.11 (m, 3H, Ar–H), H), 7.82 (d, 1H, J = 7.6 Hz, Ar–H), 8.34 (s, 1H,
thiazole
13
7
); C NMR: 189.19, 170.86, 157.64, 153.33,
coumarin
Ar–H), 7.56 (d, 2H, J = 8.8 Hz, Ar–H), 8.21 (d, 2H, 142.26, 138.95, 137.06, 132.83, 132.78, 130.71, 129.53,
+
J = 8.8 Hz, Ar–H); MS (ESI, m/z): 438 [M + H] ; 128.42, 128.33, 127.86, 127.75, 127.60, 127.11, 125.29,
Anal. calcd. for C H N O S: C, 68.64; H, 3.46; N, 124.53, 121.43, 120.00, 118.16, 115.49, 109.08, 55.77;
2
5
15
3
3
+
9
.61. Found: C, 68.47; H, 3.31; N, 9.47.
MS (ESI, m/z): 461 [M + H] ; Anal. calcd. for
C H N O S: C, 73.03; H, 3.50; N, 6.08. Found: C,
2
8
16
2
3
5
-Phenyl-3-(p-tolyl)indeno[1,2-d]thiazolo[3,2-a]-
7
3.23; H, 3.31; N, 6.27.
pyrimidin-6(5H)-one (IVe). 4-Methylphenacyl bro-
mide (1 mmol, 213.07 mg) was used as reagent.
3-(8-Methoxy-2-oxo-2H-chromen-3-yl)-5-phenyl-
Orange solid (82%, 333.33 mg); mp 267–269°C; IR: indeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one (IVi).
1
1
714 (C=O), 1647 (C=N), 1578 (C=C). H NMR: 3-(2-Bromoacetyl)-8-methoxy-2H-chromen-2-one
2
1
3
.34 (s, 3H, CH ), 6.36 (s, 1H, H4
), 6.67 (s, (1 mmol, 297.1 mg) was used as reagent. Orange solid
pyrimidine
3
H, H2
), 7.13 (t, 6H, J = 8.0 Hz, Ar–H), 7.19 (d, (81%, 397.33 mg); mp 242–244°C; IR: 1736 (C=Olactone),
thiazole
H, J = 7.6 Hz, Ar–H), 7.33 (t, 2H, J = 7.2 Hz, Ar–H), 1703 (C=Oindanone), 1644 (C=N), 1584 (C=C), 1243
13
1
7
.42 (t, 2H, J = 7.2 Hz, Ar–H); C NMR: 188.85, (C–O–C); H NMR: 3.94 (s, 3H, OCH ), 6.34 (s,
3
1
57.47, 141.47, 139.62, 132.19, 130.51, 129.25, 128.92, 1H, H4
), 6.79 (s, 1H, H2
), 6.86 (d, 1H,
thiazole
pyrimidine
1
28.39, 128.19, 125.88, 125.37, 120.89, 119.46, 105.42,
J = 7.2 Hz, Ar–H), 6.97 (t, 2H, J = 7.2 Hz, Ar–H),
+
5
8.89, 20.88; MS (ESI, m/z): 407 [M + H] ; Anal. 7.14 (t, 3H, J = 7.6 Hz, Ar–H), 7.29–7.40 (m, 5H,
calcd. for C H N OS: C, 76.82; H, 4.46; N, 6.89; Ar–H), 7.88 (s, 1H, Ar–H), 8.29 (s, 1H, H4
);
coumarin
2
6
18
2
13
Found: C, 76.68; H, 4.29; N, 6.73.
-(4-Methoxyphenyl)-5-phenylindeno[1,2-d]thiazolo-
3,2-a]pyrimidin-6(5H)-one (IVf). 4-Methoxy-
phenacyl bromide (1 mmol, 229.07 mg) was used as
reagent. Orange solid (85%, 359.12 mg); mp 248– 491 [M + H] ; Anal. calcd. for C29
50°C; IR: 1715 (C=O), 1647 (C=N), 1578 (C=C), H, 3.70; N, 5.71. Found: C, 71.23; H, 3.55; N, 5.57.
C NMR: 189.25, 170.83, 157.27, 146.31, 145.99,
42.89, 142.24, 132.99, 132.56, 130.49, 128.23, 127.48,
27.00, 125.59, 124.57, 124.38, 121.13, 120.57, 119.69,
18.78, 115.11, 108.84, 56.23, 55.62; MS (ESI, m/z):
1
3
1
[
1
+
H N O S: C, 71.01;
18 2 4
2
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 4 2020

6
18
RAJITHA et al.
-(6-Bromo-8-methoxy-2-oxo-2H-chromen-3-yl)- and clotrimazole respectively. ZOI values were mea-
3
5
-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)- sured at 150 μg/mL for compounds (IVa–l) and
one (IVj). 6-Bromo-3-(2-bromoacetyl)-8-methoxy- 30 μg/mL for standard drug. Gram-positive strains
H-chromen-2-one (1 mmol, 275.99 mg) was used as included Streptococcus pyogenes and Staphylococcus
reagent. Green solid (86%, 489.7 mg); mp 279– aureus; gram-negative, Klebsiella pneumonia and
81°C; IR: 1732 (C=O ), 1703 (C=O ), 1644 Pseudomonas aeruginosa. Fungal strains included
2
2
lactone
indanone
(
C=N), 1558 (C=C), 1243 (C–O–C), 723 (C–Br); Candida glabrata, Candida albicans, Aspergillus para-
1
siticus, and Aspergillus niger.
H NMR: 3.97 (s, 3H, OCH ), 6.35 (s, 1H, H4
),
3
pyrimidine
), 7.16 (t, 3H,
thiazole
6
.98–7.00 (m, 2H, Ar–H and H2
J = 7.2 Hz, Ar–H), 7.23 (d, 1H, J = 7.2 Hz, Ar–H),
ACKNOWLEDGMENTS
7
.32 (t, 2H, J = 8.0 Hz, Ar–H), 7.40–7.55 (m, 3H,
The authors are grateful to Dr. Busi Siddhardha,
Department of microbiology, Pondicherry University, for
antimicrobial screening. Dr. Rajitha thanks the Depart-
ment of Chemistry, Gayatri Vidya Parishad College of
Engineering (A), A.P., for providing research facilities.
Ar–H), 7.56 (s, 1H, Ar–H), 7.84 (s, 1H, H4
);
coumarin
+
MS (ESI, m/z): 570 [M + H] ; Anal. calcd. for
C H BrN O S: C, 61.17; H, 3.01; N, 4.92. Found: C,
29
17
2
4
61.05; H, 3.28; N, 4.79.
3
-(6,8-Dinitro-2-oxo-2H-chromen-3-yl)-5-phenyl-
indeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one (IVk).
3
-(2-Bromoacetyl)-6,8-dinitro-2H-chromen-2-one
1 mmol, 357.07 mg) was used as reagent. Yellow solid
82%, 451.41 mg); mp 287–289°C. IR: 1738 (C=O ),
FUNDING
(
(
Arya C.G. thanks the MHRD for providing financial
support.
lactone
1
697 (C=O
), 1619 (C=N), 1588 (C=C), 1564,
indanone
1
1
348 (NO ); H NMR: 6.40 (s, 1H, H4
), 7.00–
), 7.15 (d, 2H, J = 6.8
2
pyrimidine
COMPLIANCE WITH ETHICAL STANDARDS
This article does not contain any studies involving ani-
7
.02 (m, 2H, Ar–H and H2
thiazole
Hz, Ar–H), 7.23 (d, 1H, J = 6.8 Hz, Ar–H), 7.31 (d,
2
H, J = 7.2 Hz, Ar–H), 7.41 (d, 2H, J = 7.6 Hz, Ar– mals or human participants performed by any of the
H), 7.69 (d, 1H, J = 9.2 Hz, Ar–H), 8.14 (s, 1H, authors.
H4
), 8.51 (s, 1H, Ar–H), 8.65 (s, 1H, Ar–H);
coumarin
+
MS (ESI, m/z): 551 [M + H] ; Anal. calcd. for
Conflict of Interests
C H N O S: C, 61.09; H, 2.56; N, 10.18. Found: C,
28
14
4
7
The authors declare that they have no conflict of interest.
61.21; H, 2.37; N, 10.01.
3
-(3-Oxo-3H-benzo[f]chromen-2-yl)-5-phenylin-
deno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one (IVl).
-(2-Bromoacetyl)-3H-benzo[f]chromen-3-one (1 mmol,
17.13 mg) was used as reagent. Red solid (83%,
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