Synthesis, characterization and biological activity of new 3(4H)-quinazolinone derivatives

Article abstract of DOI:10.1134/S1070363217090237

Quinazolinylbenzoic acid 1 was used as a precursor for synthesis of many heterocyclic systems. Ethyl 4-[4-oxo-2-phenylquinazolin-3(4H)-yl]benzoate 2 upon reaction with hydrazine hydrate gave 4-[4-oxo-2-phenylquinazolin-3(4H)-yl]benzoate benzoylhydrazide 3

Full text of DOI:10.1134/S1070363217090237

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 9, pp. 2067–2072. © Pleiades Publishing, Ltd., 2017.
Synthesis, Characterization and Biological Activity
of New 3(4H)-Quinazolinone Derivatives1
A. I. El-Shenawy*
Chemistry Department, Faculty of Science, Benha University, P. O. Box 13518, Benha, Egypt
*e-mail: aielshenawy@gmail.com
Received May 23, 2017
Abstract—Quinazolinylbenzoic acid 1 was used as a precursor for synthesis of many heterocyclic systems.
Ethyl 4-[4-oxo-2-phenylquinazolin-3(4H)-yl]benzoate 2 upon reaction with hydrazine hydrate gave 4-[4-oxo-
2-phenylquinazolin-3(4H)-yl]benzoate benzoylhydrazide 3. Compound 3 on treatment with 3-nitrobenz-
aldehyde, acetyl acetone, ethyl acetoacetate, and ammonium thiocyanate yielded compounds 4–8, respectively.
Isothiocyanate 8 was used for the synthesis of other quinazoline derivatives 9–16 via the reactions with various
1
reagents. All newly synthesized quinazolinone derivatives have been characterized by H NMR, IR, and mass
spectroscopy. Most of the synthesized products were evaluated for their antibacterial and antifungal activities
and some of those demonstrated high activity.
Keywords: quinazolinylbenzoic acid, isothiocyanate cyclization, antimicrobial activity
DOI: 10.1134/S1070363217090237
4(3H)-Quinazolinone derivatives possess diverse
biological and pharmacological activities [1–6]
including antibacterial [7], antihypertensive [8],
anticonvulsant [9], anti-allergic [10], and anticancer
[11]. In continuation of our studies devoted to
chemistry of quinazoline derivatives [12–17], we
report here synthesis of new quinazoline derivatives
bearing different heterocyclic moieties using
quinazolinylbenzoic acid as the starting material. In the
drug discovery process substituted oxazoles and their
analogs have been used for the synthesis of various
biologically active molecules and drugs [18–21].
Ethyl 4-[4-oxo-2-phenylquinazolin-3(4H)-yl]ben-
zoate (2). A mixture of 1 (0.01 mol) in absolute
ethanol (40 mL) containing conc. H2SO4 (3 mL) was
refluxed for 4 h, then concentrated, cooled down and
poured onto ice. The solid residue crystallized from
ethanol to give 2. Yield 71%, mp 104–106°C. IR
spectrum, ν, cm−1: 3014 (CH aromatic), 2910 (CH
1
aliphatic), 1739, 1681 (CO), 1610 (CN). H NMR
spectrum, δ, ppm: 1.3 t (3H, CH2CH3), 4.30 q (2H,
CH2, ester), 7.30–8.01 m (13H, C6H5, C6H4). MS, m/z
[M]+: 370 (370.34). Found, %: C 74.53; H 4.82; N
7.54. C23H18N2O3. Calculated, %: C 74.59; H 4.86; N
7.57.
EXPERIMENTAL
4-(2-Phenyl-oxo-4H-quinazolin-3-yl)benzoylhyd-
razide (3). A mixture of 2 (0.01 mol) with hydrazine
hydrate (0.01 mol) was refluxed in ethanol (40 mL) for
3 h. The reaction mixture was poured onto ice-HCl and
the solid product was filtered off and crystallized from
ethanol to give 3. Yield 68%, mp 126°C. IR spectrum,
ν, cm−1: 3475–3212 (NH, NH2), 1691 (CO), 1610
The chemical reagents were purchased from Sigma-
Aldrich. TLC was carried out on pre-coated silica gel
polyester sheets (kieselgel 60 F245, 0.02 mm, Merck).
Melting points were measured uncorrected. IR spectra
in KBr were recorded on a Perkin-Elmer 298
spectrophotometer. 1H NMR spectra were measured on
a Varian Gemini 200 MHz spectrometer in DMSO-d6
using TMS as the internal reference. Mass spectra
were measured on a Jeol JMS D-300 spectrometer
operating at 70 eV. Micro-analysis was conducted on a
1106 Elemental Analyzer.
1
(CN). H NMR spectrum, δ, ppm: 2.00 s (2H, NH2),
7.35–8.01 m (13H, C6H5, C6H4), 8.00 s (1H, CONH2).
MS, m/z [M]+: 356 (356.21). Found, %: C 70.74; H
4.47; N 15.71. C21H16N4O2. C21H16N4O2. Calculated, %:
C 70.79; H 4.49; N 15.73.
N-[3-Nitrobenzylidene]-4-[2-phenyl-4-oxo-quina-
zolin-3(4H)-yl]benzoylhydrazide (4). A mixture of 3
(0.01 mol) with 3-nitrobenzaldehyde (0.01 mol) in
1 The text was submitted by the author in English.
2067

2068
EL-SHENAWY
presence of piperidine (0.5 mL) was refluxed for 4 h.
The solid formed upon cooling was filtered off and
crystallized from ethanol to give 4. Yield 63%, mp
178°C. IR spectrum, ν, cm−1: 3447 (NH), 1696, 1660
benzoyl chloride (0.01 mol) in dry acetone (30 mL),
solid ammonium thiocyanate (0.01 mol) was added.
The reaction mixture was stirred for 1 h at room tem-
perature. Ammonium chloride was precipitated in the
course of the reaction and separated by filtration,
leaving a clear solution of quinazolinyl isothiocyanate 8.
1
(CO), 1590 (CN), 1442 (NO2). H NMR spectrum, δ,
ppm: 7.40–7.90 m (17H, Ar-H), 9.92 s (1H, CH=N),
10.08 br (1H, NH). MS, m/z [M]+: 490. Found, %: C
68.67; H 3.86; N 14.29. C28H19N5O4. Calculated, %: C
68.71; H 3.89; N 14.31.
2-Phenyl-3-{4-(2-phenyl-5-thioxo)-2,4-dihydro-
1H[1,2,4]triazolidin-3-yl}phenyl-quinazoline-4(3H)-
one (9). A mixture of 8 (0.01 mol) with phenyl
hydrazine (0.01 mol) was refluxed in dry acetone for
1 h. The reaction mixture, after cooling and concentra-
tion, was filtered and the residue was crystallized from
benzene to give 9. Yield 65%, mp 213°C. IR spectrum,
ν, cm−1: 3240–2330 (NH), 1690, 1655, 1645 (CO),
3-[4-(3,5-Dimethyl-1H-pyrazole-1-carbonyl)phenyl]-
2-phenylquinazolin-4(3H)-one (5). A mixture of acid
hydrazide 3 (0.01 mol) with acetyl acetone (0.01 mol)
in presence of few drops of acetic acid was refluxed
for 4 h, then poured onto ice and filtrated. The residue
was crystallized from ethanol to give 5. Yield 59%, mp
60°C. IR spectrum, ν, cm−1: 3436 (NH), 1710, 1657
1
1605 (CN), 1257 (C=S). H NMR spectrum, δ, ppm:
1.50 s (1H, SH), 2.00 s (1H, NH cyclic), 3.5-3.7 q (2H,
CH2, cyclic), 8.03 s (1H, NH), 7.35–8.03 m (13H, Ar-
H). MS, m/z [M]+: 474. Found, %: C 71.01; H 4.00; N
14.79; S 6.75. C28H19N5OS. Calculated, %: C 71.04; H
4.02; N 14.80; S, 6.77.
1
(CO), 1605 (CN). H NMR spectrum, δ, ppm: 2.30 s
(3H, CH3, pyrazole), 2.48 s (3H, CH3, pyrazole), 6.18 s
(1H, olefinic of pyrazole),7.40–8.03 m (13H, Ar-H).
MS, m/z [M]+: 490 (490.34). Found, %: C 74.26; H
4.73; N 13.30. C28H19N5O4. Calculated, %: C 74.29; H
4.76; N 13.33.
N-(2-Mercapto-5-oxo-oxazolidin-2-yl)-4-[4-oxo-2-
phenylquinazolin-3(4H)-yl]benzamide (10). A mix-
ture of 8 (0.01 mol) with glycine (0.01 mol) in
pyridine was refluxed for 1 h. The reaction mixture
was concentrated and upon cooling down it gave the
solid product which was crystallized from acetic acid
to give 10. Yield 68%, mp 231°C. IR spectrum, ν, cm−1:
3240–2330 (NH), 2160 (SH), 1690, 1655, 1645 (CO),
3-[4-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-
carbonyl)phenyl]-2-phenylquina-zolin-4(3H)-one
(6). A mixture of compound 3 (0.01 mol) with ethyl
acetoacetate (0.01 mol) in presence of few drops of
acetic acid was refluxed for 4 h, then poured onto ice.
The residue was filtered off and crystallized from
ethanol to give 6. Yield 62%, mp 62°C. IR spectrum,
1
1605 (CN). H NMR spectrum, δ, ppm: 1.50 s (1H,
1
ν, cm−1: 1705, 1680, 1657 (CO), 1605 (CN). H NMR
SH), 2.00 s (1H, NH, cyclic), 3.5–3.7 q (2H, CH2,
cyclic), 8.03 s (1H, CONH), 7.35–8.03 m (13H, Ar-H).
MS, m/z [M]+: 474 (474.51). Found, %: C 62.85; H
3.90; N 12.21; S 6.97. C24H18N4O4S. Calculated, %: C
62.88; H 3.93; N 12.23; S, 6.99.
spectrum, δ, ppm: 1.92 s (3H, CH3, pyrazole), 2.20 s
(2H2, cyclic), 7.30–8.01 m (13H, Ar-H). MS, m/z [M]+:
423 (423.17). Found, %: C 71.06, H 4.24 N 13.23.
C25H18N4O3. Calculated, %: C 71.09, H 4.27, N 13.27.
2-Phenyl-3-[4-(5-thioxo-4,5-dihydro-1H[1,2,4]tri-
azol-3-carbonyl]phenylquinazolin-3(4H)-one (7). A
mixture of 3 (0.01 mol) with ammonium thiocyanate
(0.01 mol) was fused in an oil-bath at above melting
point of compound 3 for 30 min, then poured in cold
water. The solid residue was crystallized from ethanol
to give 7. Yield 62%, mp 180°C. IR spectrum, ν, cm−1:
3240-2330 (NH), 1710, 1665 (CO), 1605 (CN) 1237
2{3-[4-(2-Phenyl-4-oxo-4H-quinazolin-3-yl)benzo-
yl]thioureido}benzoic acid (11). A mixture of 8
(0.01 mol) with anthranilic acid (0.01 mol) was
refluxed in dry acetone for 1 h. The reaction mixture
was cooled down and the residue was crystallized from
ethanol to give 11. Yield 69%, mp 192°C. IR spec-
trum, ν, cm−1: 3500–3150 (NH), 3400–2800 br (OH),
1
1690, 1655, 1645 (CO), 1605 (CN), 1254 (C=S). H
1
(C=S). H NMR spectrum, δ, ppm: 2.00 s (1H,
NMR spectrum, δ, ppm: 4.0 s (1H, CSNH), 8.00 s (1H,
CONH), 7.35–8.03 s (17H, Ar-H), 11.03 s (1H,
COOH). MS, m/z [M]+: 521 (521.13). Found, %: C
66.90; H 3.83; N 10.75; S 6.13. C29H20N4O4S.
Calculated, %: C 66.92; H 3.85; N 10.77; S 6.15.
NHC=S), 7.00 s (1H, NNHC=S), 7.3–8.01 m (13H,
Ar-H). MS, m/z [M]+: 426 (426.39). Found, %: C
64.92; H 3.52; N 16.45. C23H15N5O2S. Calculated, %:
C 64.94; H 3.53; N 16.47.
4-(2-Phenyl-4-oxo-4H-quinazolin-3-yl)benzoyliso-
thiocyanate (8). To a stirred solution of quinazolinyl-
2-Phenyl-3-[4-(4-oxo-5-thioxo)-1,4-dihydro-2H-
quinazolin-3-carbonyl)-phenyl]-3H-quinazolin-4-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 9 2017

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY
2069
Scheme 1.
EtOH
Ar−COOH
Ar−COOEt
H2SO4
1
2
.
NH2NH2 H2O
O
H
N
NH4SCN
S
NO2
Ar−CONHNH2
Ar
N
NH
3
7
OHC
CH3COCH2CO2Et
(CH3CO)2CH2
O
O
Ar−CONHN=C
N
N
N
N
H
Ar
H3C
Ar
O
CH3
CH3
NO2
4
5
6
one (12). Compound 11 (1 g) was refluxed in acetic
anhydride for 1 h. The reaction mixture was con-
centrated and the solid residue was crystallized from
ethanol to give 12. Yield 71%, mp 161°C. IR spec-
trum, ν, cm−1: 3390 (NH), 1700 (CO), 1295 (C=S).
MS, m/z [M]+: 502 (502.33). Found, %: C 69.47; H
3.37; N 11.15; S, 6.36. C29H17N4O3S. Calculated, %: C
69.46; H 3.39; N 11.18; S, 6.39.
cooled down and the solid product was crystallized
from ethanol to give 15. Yield 80%, mp 180°C. IR
spectrum, ν, cm−1: 3240–2330 (NH), 1710, 1665 (CO),
1
1690 (CO), 1605 (CN), 1237 (C=S). H NMR spec-
trum, δ, ppm: 3.52 d (2H, CH2), 7.00 s (1H, NNHC=S),
7.3–8.01 m (13H, Ar-H), 12.8 br (1H, COOH). MS,
m/z [M]+: 475 (475.36). Found, %: C 60.62; H 3.56; N
8.85; S, 13.45. C24H17N3O4S2. Calculated, %: C 60.63;
H 3.59; N 8.84; S, 13.47.
4-[(2-Phenyl-4-oxo-4H-quinazolin-3-yl)benzoyl]-
thiocarbamic acid-o-(2-aminophen-yl) ester (13). A
mixture of 8 (0.01 mol) with o-aminophenol
(0.01 mol) in dry acetone was refluxed for 1 h. The
reaction mixture was cooled down and the solid
product was filtered off and crystallized from ethanol
to give 13. Yield 72%, mp 143°C. IR spectrum, ν,
cm−1: 3338 (NH), 1694 (CO), 1295 (C=S), 1100 (C–O).
MS, m/z [M]+: 492 (492.17). Found, %: C 68.41; H
3.85; N 11.40; S, 6.50. C28H19N4O3S. Calculated, %: C
68.43; H 3.87; N 11.41; S, 6.52.
2-Phenyl-3-[4-(4-oxo-5-thioxothiazolidin-3-carbo-
nyl)phenyl]-3H-quinazolin-4-one (16). Refluxing of
compound 15 (1 g) in acetic anhydride for 2 h led to
the product of cyclization. The solid residue was
crystallized from ethanol to give 16. Yield 79%, mp
138°C. IR spectrum, ν, cm−1: 1705, 1680, 1657 (CO),
1
1605 (CN), 1299 (C=S). H NMR spectrum, δ, ppm:
2.20 s (2H2, cyclic), 7.30–8.01 m (13H, Ar-H). MS,
m/z [M]+: 446 (446.19). Found, %: C 62.00; H 3.35; N
9.40; S, 9.41. C23H15N3O3 S2. Calculated, %: C 62.02;
H 3.37; N 9.44; S, 14.38.
N-Benzooxazol-2-yl-4-(2-phenyl-4-oxo-4H-quina-
zolin-3-yl)benzamide (14). Compound 13 (1 g) was
fused in a fusion tube for 1 h, then poured onto ice
water and the solid residue was crystallized from acetic
acid to give compound 14. Yield 76%, mp 155°C. IR
spectrum, ν, cm−1: 3320 (NH), 1676 (C=O), 1587 (C=N).
RESULTS AND DISCUSSION
Our strategy was based on the use of readily
available anthranilic acid and site-selective triple
condensation reaction for the synthesis of 3(4H)-
quinazolinone analogous. Esterification of compound 1
with absolute ethanol in presence of conc. H2SO4 gave
ethyl 4-[4-oxo-2-phenylquinazolin-3(4H)-yl]benzoate
2. Reaction of the ester 2 with hydrazine hydrate in
4-[(2-Phenyl-4-oxo-4H-quinazolin-3-yl)benzoyl-
thiocarbamoylsulfanyl]acetic acid (15). A mixture of
8 (0.01 mol) with thioglycolic acid (0.01 mol) in dry
acetone was refluxed for 1 h. The reaction mixture was
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 9 2017

2070
EL-SHENAWY
Scheme 2.
O
Ar−C−NH
N
O
NH
Ar
Ph
N
N
N
H
S
O
10
9
H2NCH2COOH
O
(1) SOCl2
(2) NH4SCN
Ar−COOH
Ar−C−N=C=S
1
8
NH2
H2N
COOH
HO
SHCH2COOH
S
O
S
O
NH2
Ar−C−HN−C−HN
Ar−C−HN−C−O
O
Ar−C−HN−CSSCH2COOH
HOOC
15
11
13
Ac2O
Ac2O
Fusion
H
S
S
O
N
O
O
O
Ar−C− N
S
Ar−C−HN
N
Ar−C−
N
O
O
14
16
12
O
.
N
Ar =
N
Ph
ethanol gave benzoylhydrazide 3. The study of
reactivity of benzoylhydrazide 3 towards aldehydes
and active methylene compounds targeted preparation
of biologically active pyrazole derivatives [22, 23].
Thus, the reaction of compound 3 with 3-nitro-
benzaldehyde afforded N-(3-nitrobenzylidene)-4-
[4-oxo-2-phenylquinazolin-3(4H)-benzoyl]hydrazide
4. Reaction of compound 3 with acetyl acetone and/or
ethyl acetoacetate afforded 3-[4-(3,5-dimethyl-1H-
pyrazole-1-carbonyl)phenyl]-2-phenylquinazolin-
4(3H)-one 5 and 3-[4-(3-methyl-4,5-dihydro-1H-pyra-
zole-3-carbonyl)phenyl]-2-phenylquinazolin-4(3H)-
one 6. Fusion of compound 3 with ammonium thio-
cyanate gave 2-phenyl-3-[4-(5-thioxo-4,5-dihydro-1H-
1,2,4-triazole-3-carbonyl)phenyl]quinazolin-4(3H)-one
7 (Scheme 1). Reaction of quinazolinylbenzoic acid 1
with thionyl chloride followed by treatment with ammo-
nium thiocyanate in dry acetone [24] gave quina-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 9 2017

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY
Antimicrobial activity of some synthesized compoundsa
2071
Bacillus
Subtilis
Rhodococcus
Equi
Salmonella
typhimurium
Escherichia
coli
Aspergillus
Niger
Penicillium
Notatum
Comp. no.
3
++
++
++
+++
+++
+++
+++
+++
+++
+++
+++
+++
–
+++
+++
+++
+++
+++
+++
+++
++
++
+++
+++
++
_
_
_
4
_
5
+++
+++
+++
+++
+++
+++
+++
+++
–
++
++
++
++
++
++
+
++
++
++
++
++
++
++
–
7
9
++
11
++
15
14
+++
++
16
++
+++
+++
–
Amoxicillin
Sulphadiazine
+++
–
–
+++
+++
a
Inhibition zone diameter: (+++) (d > 12 mm, highly active), (++) (d = 9–12 mm, moderately active), (+) (d = 6–9 mm, slightly active),
(−) (d < 6 mm, inactive).
zolinylisothiocyanate 8, which was used as a building
block for construction of biologically important
triazole, oxazole and quinazoline derivatives. Thus, the
reaction of compound 8 with phenyl hydrazine in dry
acetone gave 2-phenyl-3-[4-(2-phenyl-5-thioxo-2,5-
dihydro-1H-1,2,4-triazol-3-yl)phenyl]quinazolin-
4(3H)-one 9 (Scheme 2). Reaction of 8 with glycine
afforded N-(2-mercapto-5-oxo-oxazolidin-2-yl)-4-(4-
oxo-2-phenylquinazolin-3(4H)-yl)benzamide 10.
Reaction of 8 with anthranilic acid gave 2-{3-{4-[4-
oxo-2-phenylquinazolin-3(4H)-yl]benzoyl}thioureido}
benzoic acid 11, which underwent cyclization by
boiling in acetic anhydride to yield 3-(4-[4-oxo-1,2,3,4-
tetrahydro-quinazolin-3-carbonyl)phenyl]-2-phenyl-
quinazolin-4(3H)-one 12. Reaction of 8 with 2-amino-
phenol gave 2-amino-phenyl-4-(4-oxo-2-phenylquina-
zolin-3(4H)-yl)benzoylcarbamothioate 13, which
cyclized with formation of N-(benzoyl[d]oxazol-2-yl)-
4-[4-oxo-2-phenylquinazolin-3(4H)-yl]benzamide 14.
Reaction of 8 with thioglycolic acid gave 2-(4-[4-oxo-
2-phenylquinazolin-3(4H)-yl]phenylcarbamothioyl-
thio)acetic acid 15, which cyclized into 3-{4-[4-oxo-2-
phenylquinazolin-3(4H)-yl]benzoyl}-2-thioxothiazo-
lidin-4-one 16 by boiling in acetic anhydride. The
structures of newly synthesized derivatives were con-
firmed by elemental analysis and spectroscopic data.
subtilis, Rhodococcus Equi, and the Gram-negative
bacteria Salmonella typhimurium and Escherichia coli.
They were also evaluated for antifungal activity
against Aspergillus Niger and Penicillium Notatum.
Amoxicillin and sulphadiazine were used as standard
drugs. The agar diffusion method [25] was used for
determination of the preliminary antibacterial and
antifungal activity and the results were recorded for
each tested compound as the average diameter of
inhibition zones (d) of bacterial or fungal growth
around the disks in millimeters at concentration of
50 mg/mL in DMSO.
The synthesized products showed higher anti-
bacterial activity than antifungal activity. Only com-
pounds 9 and 15 demonstrated higher antifungal
activity against Salmonella typhimurium and com-
pounds 3 and 4 were inactive activity against Aspergillus
Niger and Penicillium Notatum.
CONCLUSIONS
Synthetic approach to the new 3(4H)-quinazolinone
derivatives is developed. The synthesis of ethyl 4-[4-
oxo-2-phenyl-quinazolin-3(4H)-yl]benzoate 2 and 4-(2-
phenyl-4-oxo-4H-quinazolin-3-yl)benzoyl isothiocyanate
8 afforded the corresponding free N-nucleo-sides. The
method is superior in simplicity and yield, compared to
alternative multistep strategies that had been reported
earlier. A series of 3(4H)-quinazolinone derivatives
Antimicrobial activity. Antimicrobial activity (see
the table) of some synthesized compounds was
screened against Gram positive bacteria Bacillus
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 9 2017

2072
EL-SHENAWY
Chem., 1997, vol. 34, p. 1669. doi 10.1002/
jhet.5570340605
were synthesized and were characterized by spec-
troscopic techniques. Antimicrobial activity of the title
compounds was evaluated against gram positive, gram
negative bacteria and fungal pathogens. Most of the
synthesized derivatives demonstrated biological
activity close to that of amoxicillin and sulphadiazine.
11. Hassanzadeh, F.,
Jafari, E., Hakimelahi, G.H.,
Khajouei, M.R.M., Jalali, M., and Khodarahmi, G.A.,
Res. Pharm. Sci., 2012, vol. 7(2), p. 87.
12. El-Shenawy, A.I. and Aly, A.A., Egypt. J. Chem., 2005,
vol. 48(6), p. 781.
ACKNOWLEDGMENTS
13. Chao, Q., Deng, L., Shih, H., Leoni, L.M., Genini, D.,
Carson, D.A., and Cottam, H.B., J. Med. Chem., 1999,
vol. 42, p. 3860. doi 10.1021/jm9805900
14. Rewcastle, G.W., Denny, W.A., Bridges, A.J., Zhou, H.,
Cody, D.R., McMichael, A., and Fry, D.W., J. Med.
Chem., 1996, vol. 38, p. 482. doi 10.1021/jm00018a008
The authors was grateful to Botany Department,
Benha University, for help and providing biological
screening.
REFERENCES
15. Glaser, T. and Traber, J., Agents Actions, 1984, vol. 15,
p. 314. doi org/10.1007/BF01972369
1. Kobayashi, S., Ueno, M., Suzuki, R., and Ishitani, H.,
Tetrahedron Lett., 1999, vol. 40, p. 2175. doi
org/10.1016/S0040-4039(99)00142-2
2. Raju, G.N., Sai, K.B., Resshma, Sudarshini, N.,
Sowmya, P.L., Nalini, Y., and Nadendla, R.R., J. Chem.
and Pharm. Research, 2015, vol. 7(5), p. 1279.
3. Gueyrard, D., Gurnel, V., Leoni, O., Palmieri, S.M., and
Rollin, P., Heterocycles, 2000, vol. 52, p. 827. doi
10.3987/COM-99-S93
4. Cao, S.L., Feng, Y.P., Jiang, Y.P., Liu, S.Y., Ding, G.Y.
and Li, R.T., Bioorg. Chem. Lett., 2005, vol. 15,
p. 1915. doi 10.1016/j.bmcl.2005.01.083
5. Rhee, H.K., Yoo, J.H., Lee, E., Kwon, Y.J., Seo, H.R.,
Lee, Y.S., and Choo, H.Y., Eur. J. Med. Chem., 2011,
vol. 46(9), p. 3900. doi org/10.1016/j.ejmech.2011.
05.061
6. Kumar, P.B.R., Murthy, S.M., and Jayaveera, K.N.,
J. Pharm. Bio. Sci., 2015, vol. 10(1), p. 30. doi
org/10.21276/ijpbs
7. Rosowesy, A., Mota, C.E., and Queener, S.F., J. Med
Chem., 1994, vol. 37, p. 4522. doi 10.1021/
jm00052a011
16. Showalter, H.D.H., Bridges, A.J., Zhou, H., Sercel, A.D.,
McMichael, A., and Fry, D.W., J. Med. Chem., 1999,
vol. 42(26), p. 5464. doi 10.1021/jm9903949
17. Navale, V., Shinde, R., Patil, S., Vibhute, A., and
Zangade, S., J. Advance Chem. Sci., 2016, vol. 2(1),
p. 201.
18. Malamas, M.S., Sredy, J., Gunawan, I., Mihan, B.,
Sawicki, D.R., Seestaller, I., Sullivan, D., and
Flam, B.R., J. Med. Chem., 2000, vol. 43, p. 995. doi
10.1021/jm990476x
19. Aaglawe, M.J., Dhule, S.S., Bahekar, S.S., Wakte, P.S.,
and Shinde, D.B., J. Korean Chem. Soc., 2003, vol. 47(2),
p. 133. doi org/10.5012/jkcs.2003.47.2.133
20. Pereira, E.R., Sancelme, M., Voldoire, A., and Prud-
homme, M., Bioorg. Med. Chem. Lett., 1997, vol. 7(19),
p. 2503. doi org/10.1016/S0960-894X(97)10007-5
21. Dharmarajan, S., Perumal, Y., Murugesan, D., and
Rathinasababathy, T., J. Antimicrom. Chem., 2007,
vol. 59(6), p. 1194. doi org/10.1093/jac/dkm085
22. Havera, H.J. and Vidrio, H.J., J. Med. Chem., 1979,
vol. 22, p. 1548. doi 10.1021/jm00198a024
23. Zhang, Y., Xu, C., Houghten, R.A., and Yu, Y., J. Comb.
Chem., 2007, vol. 9, p. 9. doi 10.1021/cc0601231
24 Caughren, S.R., WO Patent, 1997, vol. 9, p. 749.
25. Leifert, C.S., Chidburee, H.L., Hampson, S., Workman, S.,
Sigee, D., Epton, H.A.S., and Harbour, A., J. Appl.
Bacteriol., 1995, vol. 78(2), p. 97. doi 10.1111/j.1365-
2672.1995.tb02829.x
8. Jain, K.S., Bariwal, J.B., Kathiravan, M.K., Phoujdar, M.S.,
Sahne, R.S., Chauhan, B.S., Shah, A.K., and Yadav, M.R.,
Bioorg. Med. Chem., 2008, vol. 16, p. 4759. doi
org/10.1016/j.bmc.2008.02.091
9. Aly, A.A. and El-Sayed, R., Chem. Pap., 2006, vol. 60 (1),
p. 56. doi 10.2478/s11696-006-0010-3
10. Ganjee, A., Vasuderan, A., and Kisliuk, R.L., J. Het.
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