An efficient and direct synthesis of substituted 2-phenylquinoline-4-carboxamides from 3-substituted-3-hydroxyindolin-2-ones

Article abstract of DOI:10.24820/ark.5550190.p009.760

A simple and direct synthesis of substituted 2-phenylquinoline-4-carboxamides from 3-substituted-3-hydroxyindolines in presence of ammonium acetate is described. The developed protocol also allows synthesis of the carboxamide moeity directly from isatin a

Full text of DOI:10.24820/ark.5550190.p009.760

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Paper
Archive for
Arkivoc 2018, part iii, 165-173
Organic Chemistry
An efficient and direct synthesis of substituted 2-phenylquinoline-
4-carboxamides from 3-substituted-3-hydroxyindolin-2-ones
Keshri Nath Tiwari,* Rinku Choubey, Saumya Shukla, and Parul Gautam
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education
and Research (NIPER), ITI Compound, Raebareli 229 010, India
Email: keshri.tiwari@niperraebareli.edu.in
Received 06-26-2017
Abstract
Accepted 11-30-2017
Published on line 02-18-2018
A simple and direct synthesis of substituted 2-phenylquinoline-4-carboxamides from 3-substituted-3-
hydroxyindolines in presence of ammonium acetate is described. The developed protocol also allows synthesis
of the carboxamide moeity directly from isatin and acetophenone in one pot under optimized conditions. The
protocol has the merits of simple reaction conditions, easy work up process and good yields of products.
R2
O
NH2
O
NH OAc (excess)
4
R1
HO
R1
EtOH
N
O
6
-10 h
N
H
R2
9
examples
65-74% yield
Keywords: 2-Phenylquinoline-4-carboxamide, ammonium acetate, 3-hydroxyindolin-2-ones
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DOI: https://doi.org/10.24820/ark.5550190.p009.760
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Introduction
Quinoline derivatives are an important class of structural motif that is posed with diverse chemotherapeutic
1
2
3
4
activities like antimicrobial, antiviral, antimalarial and anti-inflammatory. Since the discovery of cinchophen
I) (2-phenylquinoline-4-carboxylic acid) as an analgesic drug, this pharmacophore has been extensively
(
5
-7
explored for the synthesis of antibacterial agents. The structure activity relationship of these molecules have
8
also revealed that the presence of aryl group at 2-position of quinoline ring is crucial for their bioactivity.
In particular, the 2-phenylquinoline-4-carboxamide (II) moiety have been identified and developed as
9
potent and selective non-peptide competitive antagonists for human neurokinin-3 receptor. The 2-
phenylquinolines bearing a (S)-N-(1-phenylpropyl)carboxamide functionality at the 4 position (III) represent a
class of highly potent antagonists of the NK-3 receptor. They have also been extensively studied for their
application as a ligand suitable for radiolabeling. In fact, Many of these radioactive labelled molecules have
1
0
been evaluated as radiotracer of NK-3 receptor for PET imaging studies. Quinoline-4-carboxamide analogues
(
IV) have also been studied as a potential type II binding compounds with cytochrome CYP2C9 protein which is
1
1,12
mainly responsible for drug metabolism.
Figure 1. Some biologically active 2-phenylquinoline-4-carboxamides.
Despite there being plenty of applications in medicinal chemistry, the direct synthesis of 2-
1
3-15
phenylquinoline-4-carboxamide has limited reported methods.
They are usually obtained from 2-
phenylquinoline-4-carboxylic acid (Cinchophen) which is usually synthesized by Pfitzinger or Doebner
16
reactions. While the Pfitzinger reaction involves an isatin and an aryl methyl ketone in the presence of
potassium hydroxide which allows the synthesis of 2-phenylquinoline-4-carboxylic acid whereas the Doebner
reaction gives a similar kind of product by a three-component reaction between pyruvic acid, benzaldehyde,
1
7-19
and an aniline. There are limited literature reports for the synthesis of 2-phenylquinoline-4-carboxamide.
An elegant method for one-step synthesis of 2-phenylquinoline-4-carboxylates and carboxamides from
arylimines and acrylates or acrylamides were reported under microwave conditions catalyzed by indium
20
chloride.
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As a part of our research plan aimed at developing new synthetic methods for the creation of biologically
relevant heterocyclic compounds in aqueous media, recently we have reported the synthesis of 3-substituted-
3
1
-hydroxyindolin-2-ones by aldol reactions between isatin and acetophenone catalysed by DABCO (Scheme
2
1
22
23
). The copper catalysed and Cs CO mediated efficient methods for the synthesis of 3-hydoxyindolin-2-
2
3
ones have also been documented recently. Now, we wish to report an efficient method for the direct synthesis
of 2-phenylquinoline-4-carboxamide derivatives by ring-opening and cyclization of 3-substituted-3-
hydroxyindolin-2-ones.
Scheme 1. Synthesis of 3-susbstituted-3-hydroxy-2-oxindole (3a).
Results and discussion
Initially, we began the synthesis by heating of the 3-substituted-3-hydroxyindolin-2-one (3a) in the presence of
o
excess of ammonium acetate in EtOH at 80 C (Scheme 2). After TLC indicated the complete consumption of
3
a, the solvent was evaporated, leaving a brown-colored solid. This brown solid was dissolved in a large
volume of dichloromethane with the addition of few drops of methanol. The solution was left for overnight
1
13
and the product 4a crystallized out as a white solid. The structure of 4a was confirmed by H, C NMR, IR and
mass spectral analysis. Although the TLC indicated the complete conversion of 3a into 4a, the yield of the
product was found low. It was realized by TLC that a significant amount of the product (4a) was present in the
mother liquor. We therefore purified the reaction mixture by silica gel column chromatography and the
product was isolated with 72% yield.
Scheme 2. Synthesis of 2-phenylquinoline-4-carboxamide (4a).
We also investigated the efficiency of the reaction in different solvents for optimal conditions. For this,
the reaction was performed with 3a on a 300 mg scale in various solvents (Table 1). Although the expected
product was obtained in most of the solvents, EtOH was found a better solvent with respect to reaction time
and yield.
During the synthesis of 3a, it was observed that the product separated out as solid in water and it was
2
1
almost pure. We had also found that the reaction can also be performed in EtOH. Keeping this in view, we
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planned to make this two step reaction in one pot. Therefore, isatin (1a) and acetophenone (2a) were heated
in EtOH using DABCO as a catalyst for 2 hours. After the TLC indicated the consumption of 1a and 2a, NH OAc
4
was added to the reaction mixture portion wise and the mixture heated for a further 4 hours. To our
satisfaction, the compound 4a obtained in 60% yield (Scheme 3). It was interesting to note that the portion
wise addition of ammonium acetate (4 to 5 eq.) at regular intervals of 2 hours was found more efficient that
one-time addition.
Table 1. Optimization of solvents for the synthesis of 4a from 3a
a
Entry
Solvent
EtOH
Base
Time (h)
6 h
Yield (%)
1
2
3
4
5
6
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
72
CH CN
10 h
10 h
12 h
12 h
10 h
40
3
DMF
CHCl3
THF
45
30
25
H2O
No product
a
isolated yield
Scheme 3. One pot synthesis of 2-phenylquinoline-4-carboxamide (4a).
The scope of the substrate for this transformation was studied using substituted isatins and
acetophenones (Scheme 4). It was observed that the second step of the reaction was generally prolonged by
about 3-4 times in comparison to the duration of first step. The reaction time in the table indicates the total
reaction time over both the steps (Table 2).
Scheme 4. Synthesis of 4-arylquinoline-4-carboxamides 4a-i.
As reflected in the Table 2, the electronic effect of substituents was also observed during the reaction.
The reaction time for unsubstituted isatin was found relatively less (6 h) in comparison to 5-chloro/bromo
substitution (10 h) and the yield was found less for 5-bromo isatin. It indicates that chloro/bromo substitution
at 5 position of isatin retards the reaction. For acetophenone, the yield was found maximum (74%) with 4-
methyl substitution and minimum (68%) for 4-bromo substitution. This indicates that electron donation group
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at 4-position of acetophenone is found more reactive substrate for this synthetic transformation (Table 2).
Table 2. Scope of substrate with reaction time and yield of product (4a-i)
Product (4a-i)
1
2
Entry Isatin (R ) Acetophenone (R )
Time (h)
a
(
Yield %)
4a (72)
4b (74)
4c (70)
4d (65)
4e (74)
4f (75)
4g (68)
4h (68)
4i (70)
1
2
3
4
5
6
7
8
9
H
H
H
CH3
OCH3
H
6
12
12
10
10
8
H
Cl
Cl
Cl
Cl
Br
Br
CH3
OCH3
Br
8
H
10
10
OCH3
a
Isolated yield
1
13
The characterization of all the compounds was done by H, C NMR and IR spectra as well as HRMS
+
analysis. The mass spectra of all synthesized compounds showed a characteristic [M+H] peak. The IR spectra
-
1
-1
of 4a showed characteristic two peaks of amide carbonyl (CONH ) at 1660 cm and 1588 cm and two peaks
2
-
1
-1
for NH were observed at 3373 cm and 3150 cm . A similar pattern was observed for all the other
2
1
compounds. The H NMR spectra of compound 4a showed the disappearance of –CH and OH protons which
2
were observed in 3a. The chemical shifts of all the aromatic protons of quinoline and phenyl ring were
observed in between δ 7.2 ppm to 8.5 ppm. The NH protons of amide were observed at approx. δ 8.0 ppm.
2
1
3
The C NMR showed a characteristic peak at δ 168 ppm in 4a amide carbonyl (CONH ). The melting point of
2
2
4
compound 4a was found in good agreement with the literature report.
In this way, a series of 9 molecules was synthesized and fully characterized by various spectral analysis
bearing substitution on both isatin and acetophenone. The synthesized molecules with their reaction times
and yields are given in Scheme 4 and Table 2.
A plausible route to the formation of 4a from the intermediate 3a can be explained as the ammonium
acetate decomposes to give ammonia which attacks the carbonyl to give imine (5) which undergoes
tautomerization to provide an enamine (6). The amino group then attacks the carbonyl of the indolinone to
give an intermediate pyrrolenone with aniline residue (7). Further cyclization of the aniline with imine provide
benzodiazepinone (8) which after ring-opening and release the amide group provides 4-
hydroxydihydroquinoline (9) and further elimination of water provides the product 4a. This sequence is shown
in Scheme 5. The DABCO is used as a base for aldol reaction between isatin (1a) and acetophenone (2a) in the
first step for the synthesis of 3-substituted-3-hydroxyindolin-2-one (3a).
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Scheme 5. A plausible mechanism for formation of 2-phenylquinoline-4-carboxamide (4a).
Conclusion
In summary, we have developed an efficient and direct method for the synthesis of substituted 2-
phenylquinoline-4-carboxamide by ring opening and cyclization of 3-hydroxyindolines. This method is
applicable to a wide substrate scope for both the isatin and acetophenone and provides a series of quinoline-
4
-carboxamides which represent a pharmaceutically important scaffold. The reaction conditions and work up
procedure is very simple with good yield of products. Further exploration of this methodology is currently
under way in our laboratory and findings will be reported with due course.
.
Experimental section
General. Commercially available isatins, acetophenones and ammonium acetate from Spectrochem were
used. Progress of reactions was monitored by thin layer chromatography (TLC). NMR spectra were recorded in
1
13
DMSO d at 400 MHz for H and 100 MHz for C on Bruker Avance DPX-400 MHz. Chemical shifts were
6
1
3
reported in δ (ppm) relative to DMSO-d ( C) as internal standards. Integrals are in accordance with
6
assignments, coupling constants are given in Hz. The HRMS was recorded on a JOEL-AccuTOF JMS-T100LC
Mass spectrometer having a DART source. The IR spectra were recorded on Spectrum RX-1 FTIR, Perkin Elmer.
Yields refer to quantities obtained after chromatography. Melting points of compounds were recorded on
Labindia make melting point apparatus.
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Synthesis of 2-phenylquinoline-4-carboxamide (4a)
o
A solution of 0.3 gm (1.12 mmol) of 3a and 0.432 gm of ammonium acetate (5.6 mmol) was heated to 80 C in
EtOH for 6 hours. The ammonium acetate was added in portion wise at regular interval. After the TLC
indicated the complete consumption of 3a, the solvent was evaporated on rotatory evaporator to provide
dark brown solid which was purified by silica gel column chromatography using hexane:EA (7:3) as an eluent to
provide 4a as white colour solid. All the experiments for substituted compounds were performed in similar
manner. The reaction times and yields of all the synthesized compounds are mentioned in the Results and
Discussion section of the paper.
ᴏ
2
1
8
3
1
2
3
1
3
1
2
3
-phenylquinoline-4-carboxamide (4a). White solid; 72%, 195 mg, mp 190-191 C; IR (KBr): ѵ 3373, 3150,
max
-
1
1
669, 1588 cm ; H NMR (400 MHz, DMSO-d ): δ 8.31 (dd, J 8 Hz, 4 Hz, 2H, Ar-H), 8.27 (d, J 8 Hz, 1H, Ar-H),
6
.16 (s, 1H), 8.13 (d, J 8 Hz, 1H, Ar-H) 7.93 (bs 1H, NH) 7.82 (t, J 8 Hz, 1H) 7.65 (t, J 8 Hz, 1H, Ar-H) 7.60-7.53 (m,
1
3
H, Ar-H); C NMR (100 MHz, DMSO-d ): δ 168.6, 155.7, 147.9, 143.0, 138.2, 130.0, 129.8, 129.4, 128.8, 127.2,
6
+
27.0, 125.4, 123.2, 116.5; HRMS (ESI) m/z for C H N O [M+H] , calcd., 249.1027, found, 249.1053
1
6 13 2
ᴏ
-(p-tolyl)quinoline-4-carboxamide (4b). Light yellow solid; 74%, 206 mg ; Mp 203-205 C; IR (KBr): ѵ 3355,
max
-
1 1
152, 1669, 1596 cm ; H NMR (400 MHz, DMSO-d ): δ 8.31 (bs, 1H) 8.26-8.21 (m, 3H, Ar-H), 8.11 (t, J 8 Hz,
6
H, Ar-H), 7.92 (bs, 1H, NH), 7.80 (t, J 8 Hz, 1H, Ar-H) 7.63 (t, J 8 Hz, 1H, Ar-H) 7.38 (d, J 8 Hz, 1H, Ar-H) 2.40 (s,
1
3
H, CH ); C NMR (100 MHz, DMSO-d ): δ 168.6, 155.6, 147.9, 142.9, 139.5, 135.5, 130.0, 129.3, 127.1, 126.8,
3
6
+
25.4, 123.1, 116.2, 20.8; HRMS (ESI) m/z for C H N O [M+H] , calcd., 263.1184, found, 263.1164
1
7 15 2
ᴏ
-(4-methoxyphenyl)quinoline-4-carboxamide (4c). White solid; 70%, 196 mg; mp 235-237 C; IR (KBr): ѵ
max
-
1
1
336, 3155, 1665, 1584 cm ; H NMR (400 MHz, DMSO-d ): δ 8.30-8.22 (m, 3H, Ar-H), 8.23 (d, J 12 Hz, 1H, Ar-
6
H) 8.11 (bs, 1H) 8.08 (d, J 8 Hz, 1H, Ar-H), 7.91 (bs, 1H, NH) 7.79 (t, J 8 Hz, 1H, Ar-H), 7.60 (t, J 8 Hz, 1H, Ar-H),
1
3
7
.12 (d, J 8 Hz, 2H, Ar-H), 3.86 (s, 3H, OCH ); C NMR (100 MHz, DMSO-d ): δ 168.7, 160.8, 155.4, 147.9, 142.8,
3 6
+
1
30.7, 129.9, 129.2, 128.7, 126.5, 125.4, 122.9,116.0, 114.2, 55.3 HRMS (ESI) m/z for C H N O [M+H] ,
17 15 2 2
calcd., 279.1133, found, 279.1144
ᴏ
6
-chloro-2-phenylquinoline-4-carboxamide (4d). White solid; 65%, 182 mg; mp 270-272 C; IR (KBr): ѵ
max
-
1 1
3
372, 3153, 2980, 1647, 1584 cm ; H NMR (400 MHz, DMSO-d ): δ 8.41 (bs, 1H), 8.35 (d, J 4 Hz, 1H, Ar-H),
6
8
.32 (d, J 4 Hz, 2H, Ar-H), 8.26 (s, 1H Ar-H), 8.15 (d, J 8 Hz, 1H, Ar-H), 8.00 (bs, 1H, NH), 7.84 (dd J 8 Hz, 4Hz,
1
3
1
H, Ar-H), 7.61-7.54 (m, 3H, Ar-H) C NMR (100 MHz, DMSO-d ) :δ 168.0, 156.3, 146.5, 141.5, 137.8, 131.6,
6
+
1
31.5, 130.6, 130.1, 128.9, 127.3, 124.2, 124.0, 117.8 HRMS (ESI) m/z for C H ClN O [M+H] , calcd.,
1
6
12
2
2
83.0638, found, 283.0645
ᴏ
6
-chloro-2-(p-tolyl)quinoline-4-carboxamide (4e). White solid; 74%, 208 mg; mp 242-244 C; IR (KBr): ѵ
max
-
1 1
3
355, 3150, 1648, 1584 cm ; H NMR (400 MHz, DMSO-d ) δ 8.40 (bs, 1H), 8.33 (d, J 4 Hz, 1H, Ar-H), 8.22 (d, J
6
8
Hz, 2H, Ar-H), 8.12 (d, J 12 Hz, 1H, Ar-H), 7.99 (bs, 1H, NH), 7.83 (dd, J 8 Hz, 4 Hz, 1H, Ar-H), 7.39 (d, J 8 Hz,
1
3
2
H, Ar-H), 2.40 (s, 3H, CH ); C NMR (100 MHz, DMSO-d ) δ 168.3, 155.2, 147.3, 142.9, 127.8, 131.2, 131.0,
3 6
+
1
29.3, 126.4, 127.1, 124.6, 124.1, 116.4, 20.6; HRMS (ESI) m/z for C H ClN O [M+H] , calcd., 297.0794,
17 14 2
found, 297.0761
ᴏ
6
-chloro-2-(4-methoxyphenyl)quinoline-4-carboxamide (4f). White solid; 75%, 212 mg; mp 265-267 C; IR
-
1 1
(KBr): ѵmax 3389, 3155, 2980, 1650, 1578 cm ; H NMR (400 MHz, DMSO-d ) δ 8.39 (bs, 1H), 8.32 (d, J 4 Hz, 1H,
6
Ar-H), 8.29 (d, J 8 Hz, 1H, Ar-H), 8.21 (s, 1H, Ar-H), 8.10 (d, J 8 Hz, 1H, Ar-H), 7.98 (bs, 1H, NH), 7.81 (dd, J 8 Hz,
1
3
4
1
Hz, 1H, Ar-H), 7.13 (d, J 8 Hz, 2H, Ar-H), 3.86 (s, 3H, OCH ); C NMR (100 MHz, DMSO-d ) δ 168.1, 161.0,
3 6
56.0, 146.5, 141.3, 131.4, 131.0, 130.4, 130.2, 128.7, 124.2, 123.7, 117.3, 114.3, 55.3; HRMS (ESI) m/z for
+
C H ClN O [M+H] , calcd., 313.0743, found, 313.0736
1
7
14
2 2
ᴏ
2
-(4-bromophenyl)-6-chloroquinoline-4-carboxamide (4g). White solid; 68%, 193 mg; mp 260-262 C; IR
-
1 1
(
KBr): ѵmax 3365, 3180, 2980, 1655, 1586 cm ; H NMR (400 MHz, DMSO-d ) δ 8.41 (bs, 1H), 8.35 (d, J 4 Hz,
6
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1
H, Ar-H), 8.28 (t, J 4 Hz, 3H, Ar-H), 8.15 (d, J 8 Hz, 1H, Ar-H), 8.02 (bs, 1H, NH), 7.85 (dd, J 8 Hz, 4 Hz, 1H, Ar-
1
3
H), 7.79 (d, J 8 Hz, 2H, Ar-H); C NMR (100 MHz, DMSO-d ) δ 172.3, 167.9, 155.2, 146.4, 141.7, 136.9, 131.9,
6
+
1
3
6
3
8
1
1
3
6
31.6, 130.7, 129.3, 124.3, 123.9, 117.6 HRMS (ESI) m/z for C H BrClN O [M+H] , calcd., 360.9743, found,
16 11 2
60.9755
-bromo-2-phenylquinoline-4-carboxamide (4h). White solid; 68%, 192 mg; mp 276-278 C; IR (KBr): ѵ
ᴏ
max
-
1
1
367, 3181, 2980, 1648, 1584 cm ; H NMR (400 MHz, DMSO-d ): δ 8.51 (d, J 4 Hz, 1H, Ar-H), 8.41 (bs, 1H),
6
.32 (d, J 8 Hz, 2H, Ar-H), 8.25 (s, 1H, Ar-H), 8.08 (d, J 12 Hz, 1H, Ar-H), 8.00 (bs, 1H, NH), 7.95 (dd, J 8 Hz, 4Hz,
1
3
H, Ar-H), 7.60-7.55 (m, 3H, Ar-H); C NMR (100 MHz, DMSO-d ) δ 168.0, 156.4, 146.7, 141.4, 137.8, 133.1,
6
+
31.7, 130.1, 128.9, 127.5, 127.3, 124.5, 120.2, 117.7; HRMS (ESI) m/z for C H BrN O [M+H] , calcd.,
1
6
12
2
27.0132, found, 327.0138
ᴏ
-bromo-2-(4-methoxyphenyl)quinoline-4-carboxamide (4i). White solid; 70%, 199 mg; mp 186-188 C; IR
-
1
1
(KBr): ѵmax 3375, 3180, 2980, 1650, 1578 cm ; H NMR (400 MHz, DMSO-d ) δ 8.46 (s, 1H, Ar-H), 8.39 (bs, 1H),
6
8
.29 (dd, J 8 Hz, 2H, Ar-H), 8.20 (s, 1H, Ar-H), 8.02 (d, J 8 Hz, 1H, Ar-H), 7.98 (bs, 1H, NH), 7.92 (d, J 8 Hz, 1H, Ar-
1
3
H), 7.12 (d, J 12 Hz, 2H, Ar-H), 3.86 (s, 3H, OCH3) C NMR (100 MHz, DMSO-d ) δ 168.5, 156.2, 146.2, 142.4,
6
+
1
3
30.1, 129.7, 128.2, 126.9, 125.8, 122.6, 116.2, 114.8, 55.6 HRMS (ESI) m/z for C H BrN O [M+H] , calcd.,
17 14 2 2
57.0238, found, 357.0276
Acknowledgments
R.C., S.S., and P.G. are thankful to the Department of Pharmaceuticals, Ministry of Chemical and Fertilizers,
Govt. of India for providing fellowship. The authors are thankful to Dr. S. J. S. Flora, Director, NIPER, Raebareli
for his support and encouragement in carrying out this research work. SAIF-CSIR-CDRI, Lucknow is greatly
acknowledged for providing spectral data NIPER-R/Communication/020.
References
1
2
3
.
.
.
Garudachari, B.; Satyanarayana, M.N.; Thippeswamy, B.; Shivakumar, C. K.; Shivananda, K. N.; Hegde, G.;
Isloor, A. M. Eur. J. Med. Chem. 2012, 54, 900.
https://doi.org/10.1016/j.ejmech.2012.05.027
Velu, A. B.; Chen, G. W.; Hsieh, P. T.; Horng, J. T.; Hsu, J. T.; Hsieh, H. P.; Chen, T. C.; Weng, K. F.; Shih, S.
R. Antivir. Res. 2014, 112, 18.
https://doi.org/10.1016/j.antiviral.2014.10.003
Boa, A. N.; Canavan, S. P.; Hirst, P. R.; Ramsey, C.; Stead, A. M.; McConkey, G. A. Bioorg. Med. Chem.
2
005, 13, 1945.
https://doi.org/10.1016/j.bmc.2005.01.017
4
5
.
.
Zarghi, A.; Ghodsi, R. Bioorg. Med. Chem. 2010, 18, 5855.
https://doi.org/10.1016/j.bmc.2010.06.094
Dinakaran, M.; Senthilkumar, P.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Med. Chem. 2008, 4,
4
82.
https://doi.org/10.2174/157340608785700225
6
.
Strigacova, J.; Hudecova, D.; Varecka, L.; Lasikova, A.; Vegh, D. Folia Microbiol. 2000, 45, 305.
https://doi.org/10.1007/BF02817551
©
Page 172
ARKAT USA, Inc

Arkivoc 2018, iii, 165-173
Tiwari, K. N. et al.
7
8
.
.
Wang, X.; Xie, X.; Cai, Y.; Yang, X.; Li, J.; Li, Y.; Chen, W.; He, M. Molecules 2016, 21, 340.
https://doi.org/10.3390/molecules21030340
Sabatini, S.; Gosetto, F.; Iraci, N.; Barreca, M. L.; Massari, S.; Sancineto, L.; Manfroni, G.; Tabarrini, O.;
Dimovska, M.; Kaatz, G. W.; Cecchetti, V. J. Med. Chem. 2013, 56, 4975.
https://doi.org/10.1021/jm400262a
9
.
Giardina, G. A. M.; Sarau, H. M.; Farina, C.; Medhurst, A. D.; Grugni, M.; Foley, J. J.; Raveglia, L. F.;
Schmidt, D. B.; Rigolio, R.; Vassallo, M.; Vecchietti, V.; Hay, D. W. P. J. Med. Chem. 1996, 39, 2281.
https://doi.org/10.1021/jm9602423
1
1
1
1
1
1
1
1
0. Bennacef, I.; Perrio, C.; Lasne, M. C.; Barre, L. J. Org. Chem. 2007, 72, 2161.
https://doi.org/10.1021/jo062285p
1. Peng, C.; Cape, J. L.; Rushmore, T.; Crouch, G. J.; Jones, J. P. J. Med. Chem. 2008, 51, 8000.
https://doi.org/10.1021/jm8011257
2. Dahal, U. P.; Joswig-Jones, C.; Jones, J. P. J. Med. Chem. 2012, 55,280.
https://doi.org/10.1021/jm201207h
3. Gopalsamy, A.; Pallai, P. V. Tetrahedron Lett. 1997, 38, 907.
https://doi.org/10.1016/S0040-4039(96)02456-2
4. Aboul-Enein, H. A.; Ibrahim, S. A. J. Fluorine Chem. 1992, 59, 233.
https://doi.org/10.1016/S0022-1139(00)82415-X
5. Rapport, M. M.; Senear, A. E.; Mead, J. F.; Koepfli, J. B. J. Am. Chem. Soc. 1946, 68, 2697.
https://doi.org/10.1021/ja01216a085
6. Manske, R. H. Chem. Rev. 1942, 30, 113.
https://doi.org/10.1021/cr60095a006
7. Beilavsky, J. Collec. Czech. Chem. Comm. 1977, 42 (9), 2802.
https://doi.org/10.1135/cccc19772802
1
1
8. Mishra, P.;Agarawal, R. K.; Maini, U. K. Indian J. Pharm. Sci. 1988, 50, 269.
9. M. N. Zemtsova, A. V. Zimichev, and P. L. Trakhtenberg Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol.
2
005, 48(4), 3.
2
2
0. Duvelleroy, D.; Perrio, C.; Parisel O.; Lasne, M.-C. Org. Biomol. Chem. 2005, 3794.
https://doi.org/10.1039/b509400c
1. Tiwari, K. N.; Bora, D.; Chauhan, G.; Yadav, D.; Sharma, K.; Thakur, A.; Singh, L.; Tripathi, V. Synth.
Commun. 2016, 46, 620.
https://doi.org/10.1080/00397911.2016.1160411
2
2
2. Wang, B.; Zhu, J.; Wei, Y.; Luo, G.; Qu, H.; Liu, Liang-X. Syn. Comm. 2015, 45, 2841.
https://doi.org/10.1080/00397911.2015.1111383
3. Bai, M.; You, Y.; Chen, Yong-Z., Xiang, Guang-Y.; Xu, Xiao-Y.; Zhang, Xiao-M., Yuan, Wei-C. Org. Biomol.
Chem. 2016, 14, 1395.
https://doi.org/10.1039/C5OB02391B
2
4. Wadher, S. J.; Karande, N. A.; Borkar, D. S.; Yeole, P. G. Int. J. Chem. Tech. Res. 2009, 1, 1297.
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