An efficient synthesis of pyrazolo[3,4- b]quinolin-3-amine and benzo[b][1,8]naphthyridine derivatives

Article abstract of DOI:10.3390/12030361

2-Oxo-4-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (10) reacted with hydrazine hydrate, phenylisothiocyanate or benzoyl chloride to give derivatives 12, 13 and 15, respectively. The latter two products were treated with hydrazine hydrate to affo

Full text of DOI:10.3390/12030361

Molecules 2007, 12, 361-372
molecules
ISSN 1420-3049
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Full Paper
An Efficient Synthesis of Pyrazolo[3,4- b]quinolin-3-amine and
Benzo[b][1,8]naphthyridine Derivatives
Yehya M. Elkholy
Chemistry Department, Faculty of Science, Helwan University, Ain-Helwan, Cairo, Egypt; E-mail:
y_elkholy@yahoo.com
Received: 24 January 2007; in revised form: 10 February 2007 / Accepted: 21 February 2007 /
Published: 8 March 2007
Abstract: 2-Oxo-4-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (10) reacted
with hydrazine hydrate, phenylisothiocyanate or benzoyl chloride to give derivatives 12,
13 and 15, respectively. The latter two products were treated with hydrazine hydrate to
afford pyrozole[3,4-b]quinolines derivatives 14 and 16, respectively. Compound 10 also
reacted with acetonitrile dimer or malononitrile dimer to yield benzo[b][1,8]-
naphthyridine derivatives. A single crystal X-ray crystallographic analysis was performed
on compound 10, confirming its structure.
Keywords: Hexahydroquinoline, hydrazine hydrate, urea, acetonitrile or malononitrile
dimer, X-ray crystal structure.
Introduction
Tetrahydroquinolines are important building blocks in synthetic heterocyclic chemistry and their
use in the preparation of pyrazolo[3,4-b]quinolines and benzo[b][1,8]naphthyridines derivatives has
been reported recently [1-6]. Pyrazolo[3,4-b]quinoline derivatives are used as pharmaceutical agents
and as inhibitors of oncogenic Ras [7,8]. Interesting pharmacological properties have also been
associated with benzo[b][1,8]naphthyridine derivatives, which posses antitumor, trypanocidal and
DNA binding properties [9,10] and are antimicrobial agents [11]. In continuation of this work, we
report herein a synthesis of pyrazolo[3,4-b]quinoline and benzo[b][1,8]naphthyridine derivatives
utilizing the hexahydroquinoline 10 as starting material.

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Molecules 2007, 12
Results and Discussion
Treatment of cyclohexanone 1 with the α,β-unsaturated nitrile derivative 2 in the presence of
ammonium acetate afforded 2-oxo-4-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (10). The
structure of 10 was assigned on the basis of its elemental analyses and x-ray crystal structure (Scheme
1, Figure 1 and Table 1).
Scheme 1
O
CN
+
Ph
CO2Et
2
1
- +
CH3COONH4
EtOH /
Ph
H
Ph
H
CO2Et
N
CN
..
C
..
C
O
OEt
N
N
H2
H2
3
7
Ph
H
Ph
H
CO2Et
NH
CN
N
H
OEt
OH
N
H
4
8
- EtOH
Ph
Ph
H
H
CO2Et
NH2
CN
O
N
H
N
H
5
9
-H2 (O)
Ph
-H2 (O)
Ph
CO2Et
NH2
CN
O
N
N
H
6
10

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Molecules 2007, 12
Figure 1. ORTEP diagram of compound 10.
Table 1. Crystal data and structure refinement for compound 10.
Empirical formula
Formula weight
C16H14N2O
250.301
Temperature
298 K
Wavelength
0.71073A
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
a = 12.7092 (6)Å
b = 5.8821 (3)Å
c = 18.2257 (12)Å
α = 90.00°
β = 101.455 (2)°
1335.36 (13)Å3
4, 1.240 Mg/m3
0.08 mm-1
Volume
Z, Calculated density
Absorption coefficient
F(000)
236
Crystal size
1.00 x 0.22 x 0.16 mm
Kappa CCD
Diffractometer
Θ Rang (0)
2.910—27.485 °
-16<=h<=16, -6<=k<=7, -23<=1<=22
2323<=l<=222
Limiting indices
Reflections collected / unique 3473 / 1103 [R(int) = 0.035]
Absorption correction
Refinement method
None
Full-matrix least-squares on F2
1102/ 0 / 172
Data / restraints / parameters
Goodness-of-fit on F2
2.291
Final R indices [I>3sigma(I)] R1 = 0.172, wR2 = 0.119
R indices (all data)
R1 = 0.051, wR2 = 0.139
0.046(2)
0.049 and -0.50eÅ3
Extinction coefficient
Largest diff. peak and hole

364
Molecules 2007, 12
Compound 10 reacted with hydrazine hydrate in absolute ethanol to afford pyrazolo[3,4-
b]quinoline derivative 12 through elimination of a water molecule from intermediate 11 (Scheme 2).
Scheme 2
Ph
Ph
NH2
CN
O
NH2.NH2
EtOH /
N
NH2
OH
N
H
N
10
11
Ph
NH2
- H2O
N
N
N
H
12
When the hexahydroquinoline 10 was treated with phenylisothiocyanate, it afforded a single
product 13 (Scheme 3).
Scheme 3
Ph
CN
PhNCS
10
DMF/TEA
O
N
NH2.NH2
CSNHPh
13
Ph
NH2
N
N
N
CSNHPh
Ph
14
CN
O
PhCOCl
pyridine
N
NH2.NH2
COPh
15
Ph
NH2
PhCOCl
pyridine
N
12
N
N
COPh
16

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Molecules 2007, 12
Treatment of a suspension of the latter product with hydrazine hydrate, under reflux, afforded 3-
amino-N,4-diphenyl-5,6,7,8-tetrahydropyrazolo[3,4-b]quinolin-9-carbothioamide (14). An alternative
method for preparing compound 14 involves treating compound 12 with phenyl isothiocyanate under
similar conditions. Similarly, when compound 10 was treated with benzoyl chloride, it afforded
hexahydroquinaline derivative 15. Treatment of 15 with hydrazine hydrate, under reflux, afforded 3-
amino-5,6,7,8-tetrahydro-4-phenyl-pyrazolo[3,4-b]quinoline-9-yl)(phenyl)methanone (16), which can
also be obtained by an independent method through treatment of compound 12 with benzoyl chloride
(Scheme 3). Compound 10 reacted phenylthiosemicarbazide 17 [12] in absolute ethanol/sodium
ethoxide to afford 3-amino-5,6,7,8-tetrahydro-N,4-diphenylpyrazolo[3,4-b]quinoline-1-carbothioamide
(19) via the cyclodehydration of intermediate 18 (Scheme 4 ).
Scheme 4
S
EtOH
/EtONa
Ph
H2N - NH-C- NHPh
+
10
17
NH2
OH
S
N-NH-C-NHPh
N
18
- H2O
NH2
Ph
N
N
N
CSNHPh
19
Compound 10 reacted with urea or thiourea in absolute ethanol/sodium ethoxide for 5h to afford 4-
amino-5-phenyl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-2(1H)one / -2(1H)thiones 22a,b through
the intermediate 21 via the elimination of a water molecule (Scheme 5).
Scheme 5
Ph
N
NH2
X
N
EtOH
/
X
+
10
EtONa
H2N
NH2
NH2
OH
20
21
Ph
N
NH2
- H2O
N
X
N
H
22
X
a O
b S

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Molecules 2007, 12
In addition, compound 10 was refluxed with malononitrile to afford 4-aminobenzo[b]-
[1,8]napthyridine-3-carbonitrile (26) via the intermediates 24 and 25, as confirmed by elemental
analysis, 1H- and 13C-NMR (Scheme 6).
Scheme 6
Ph
CN
CH2
CN
23
CN
O
+
N
H
EtOH / TEA
10
Ph
N
NH2
Ph
NH2
O
Ph
N
NH2
CN
CN
CN
NH
CN
C
..
OH
O
N
H
N
26
25
24
Hexahydroquinoline derivative 10 reacted with acetonitrile dimer (3-iminobutanenitrile) or
malononitrile dimer (2-aminoprop-1-ene-1,1,3-tricarbonitrile) to afford 4-amino-benzo[b][1,8]
napthyridinecarbonitrile derivatives 29 and 32. These reactions proceed by addition of the active
methylene group to the cyano group to give the intermediate 28 and 31, which undergo cyclization via
the elimination of a water molecule. The structures of the isolated product were confirmed by
elemental and spectral analyses.
Scheme 7
NH
+
10
H3C
CH2CN
EtOH/TEA
27
CN
H2N
NC
.
Ph
N
NH2
EtOH / TEA
CN
CN
C
30
C-CH3
NH
OH
Ph
NH2
CN
28
CN
OH
- H2O
NH2
N
CN
H2N
Ph
N
31
CN
- H2O
N
CH3
29
Ph
N
NH2
CN
Ph
N
NH2
CN
CN
CN
N
CN
N
CN
H
32

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Molecules 2007, 12
The target ring system 35 was synthesized by reaction of 10 with cyanoacetohydrazide 33 through
the intermediate 34 via elimination of a water molecule (Scheme 8).
Scheme 8
O
+
10
H2NNH
CH2CN
.
EtOH/pip.
NH2
33
Ph
N
Ph
N
NH2
N
CN
CN
O
C
- H2O
C=O
OH
34
NHNH2
NH2
35
Experimental
General
All melting points are uncorrected. Elemental analyses were carried out in the Microanalytical
Center, Cairo University, Giza, Egypt. IR spectra (KBr) were recorded on Pye Unicam SP 1200
Spectrophotometer. 1H-NMR spectra were recorded in CDCl3 or DMSO-d6 on a 90 MHz Varian NMR
Spectrometer using TMS as an internal standard and chemical shifts are expressed as δ ppm units. The
homogeneity of all compounds synthesized was checked by TLC on 2.0 cm x 6.0 cm aluminum sheets
recoated with silica gel 60 containing a fluorescent indicator, to a thickness of 0.25µm.
Characterization data of the various compounds prepared are given in Tables 2 and 3.
2-Oxo-4-phenyl-1,2 ,5,6,7,8-hexarahydroquinoline–3–carbonitrile (10).
A solution of cyclohexanone (1, 0.01 mol) in absolute ethanol (30 mL) containing excess
ammonium acetate and the arylidene derivative 2 (0.01 mol) was heated under reflux for 3-5 h. The
solid material which separated during heating was collected by filtration and recrystallized from
ethanol to yield the hexahydroquinoline derivative 10.
5,6,7,8-Tetrahydro-4-phenyl-1H-pyrazolo[3,4-b]quinolin-3-amine (12)
A mixture of 10 (0.005 mol) and hydrazine hydrate (0.005 mol) in absolute ethanol (30 mL) was
refluxed for 4 h. and the reaction mixture was left at room temperature overnight and then poured into
ice/cold water to complete precipitation. The product was filtered off and recrystallized from dry
benzene to give compound 12.

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Molecules 2007, 12
3-Cyano-5,6,7,8-tetrahydro-2-oxo-N,4-diphenylquinoline-1(2H)-carbothioamide (13)
A mixture of 10 (0.005 mol) and phenylisothiocyanate (0.005 mol) in dimethylformamide
containing a catalytic amount of triethylamine (4 drops) was refluxed for 5 h. and then left to cool to
room temperature. The reaction mixture was poured into cold water for complete precipitation, then
the solids were filtered off, washed with water, dried well and recrystallized from aqueous methanol to
give compound 13.
3-Amino-N,4-diphenyl-5,6,7,8-tetrahydro-pyrazolo[3,4-b]quinolin-9-carbothioamide (14)
A mixture of 13 (0.01 mol) and hydrazine hydrate (0.01 mol) in absolute ethanol (30 mL) was refluxed
for 3 h. and the reaction mixture was left at room temperature overnight and then poured into ice/cold
water to complete precipitation. The product was filtered off and recrystallized from dry benzene to
give compound 14.
(3-Cyano-5,6,7,8-tetrahydro-2-oxo-4-phenylquinoline)(phenyl)methanone (15)
Benzoyl chloride (0.01 mol) was added to a solution of 10 (0.01 mol) in dry pyridine (30 mL) and
the mixture was refluxed on a water bath for 5 h., then left to cool to room temperature and poured into
ice cold water and neutralized by diluted hydrochloric acid for complete precipitation. The separated
material was collected by filtration, washed with water, dried well and recrystallized from acetic acid
to yield compound 15.
(3-Amino-5,6,7,8-tetrahydro-4-phenylpyrazolo[3,4-b]quinoline-9-yl)(phenyl)methanone (16)
A mixture of 15 (0.01 mol) and hydrazine hydrate (0.01 mol) in absolute ethanol (30 mL) was refluxed
for 3 h. and the reaction mixture was left at room temperature overnight and then poured into ice/cold
water to complete precipitation. The product was filtered off and recrystallized from dry benzene to
give compound 16.
General procedure for the synthesis of 3–amino–5,6,7,8-tetrahydro-N,4-diphenylpyrazolo[3,4-b]-
quinolin-1-carbothioamide (19), 4-amino-6,7,8,9-tetrahydro-5-phenylpyrimido[4,5-b]quinolin-2(1H)-
one (22a) and 4-amino-6,7,8,9-tetrahydro-5-phenylpyrimido[4,5-b]quinolin-2(1H)thione (22b).
A mixture of 10 (0.005 mol) and phenylthiosemicarbazide (0.005 mol), urea (0.005 mol) or
thiourea (0.005 mol) in absolute ethanol (20 mL) containing sodium ethoxide (0.005 mol) was refluxed
for 6 h. The reaction mixture was left to cool to room temperature, then poured into ice cold water (50
mL) and neutralized with dilute hydrochloric acid; the separated material was filtered off and
recrystallized from ethanol to give compounds 19, 22a or 22b.

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Molecules 2007, 12
4-Amino-1,2,6,7,8,9-hexahydro-2-oxo-5-phenyl-benzo[b][1,8]naphthyridin-3-carbonitrile (26).
To a solution of 10 (0.005 mol) in absolute ethanol (30 mL), triethylamine(5 mL) malononitrile
(0.005 mol) was added and the reaction mixture was refluxed for 6 h., then left to cool to room
temperature, poured into cold water and neutralized with diluted hydrochloric acid to complete
precipitation. The solid obtained was filtered off, washed with water, dried well and recrystallized
from methanol to give compound 26.
General procedure for the synthesis of 4-amino-6,7,8,9-tetrahydro-2-methyl-5-phenylbenzo[b][1,8]-
naphthyridin-3-carbonitrile (29) and 4-amino-2-(dicyanomethylene)-1,2,6,7,8,9-hexahydro-5-phenyl-
benzo[b][1,8] naphthyridin-3-carbonitrile (32).
An equimolar mixture of 10 (0.005 mol) and acetonitrile dimmer (3-iminobutanenitrile, 27, 0.005
mol) or malononitrile dimer (2-aminoprop-1-ene-1,1,3-tricarbonitrile, 30, 0.005 mol) in absolute
ethanol (30 mL) in the presence of a few drops of triethylamine (4 drops) was refluxed for 6 h. The
reaction mixture was left to cool and poured into cold water for complete precipitation. The separated
solid was filtered off, washed with water, dried well and recrystallized from ethanol to give
compounds 29 or 32.
1,4-Diamino-1,2,6,7,8,9-hexahydro-2-oxo-5-phenylbenzo[b][1,8] naphthyridin-3-carbonitrile (35)
A few drops of pipridine were added to a solution of 10 (0.005 mol) and cynanoacetohydrazide
(0.005 mol) in absolute ethanol (30 mL) and the reaction mixture was refluxed for 5 h., then left to
cool. The product was filtered off, washed with water, dried well and recrystallized from ethanol to
give compound 35.
Table 2 Physical properties and elemental analyses of the new compounds.
Formula
(mw)
Analysis % Calcd. (Found)
Compd.
M.P.°C
C
H
N
S
Cl
C16H14N2O
(250.30)
76.78
5.64
11.19
(11.46)
21.20
(21.49)
10.90
(11.15)
17.52
(17.70)
7.90
10
12
13
14
15
16
275
225
240
192
216
290
–
–
(77.02)
72.70
(5.82)
6.10
C16H16N4
(264.33)
–
(73.00)
71.66
(6.46)
4.97
C23H19N3SO
(385.47)
8.32
(8.45)
8.02
–
(71.89)
69.14
(5.04)
5.29
C23H21N5S
(399.50)
–
–
–
(69.39)
77.95
(5.56)
5.12
(8.34)
C23H18N2O2
(354.41)
–
–
(78.24)
74.98
(5.47)
5.47
(8.04)
15.21
(15.77)
C23H20N4O
(368.44)
(75.27)
(5.79)

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Molecules 2007, 12
Table 2. Cont.
Formula
(mw)
Analysis % Calcd. (Found)
Compd.
M.P.°C
C
H
N
S
Cl
C23H21N5S
(399.50)
69.15
5.30
17.53
8.03
(8.32)
19
22a
22b
26
223
207~209
185~186
167~168
198
–
(69.44)
69.85
(5.43)
5.52
(17.81)
19.16
C17H16N4O
(292.34)
−
–
–
–
–
–
–
(69.79)
66.21
(5.62)
5.23
(19.53)
18.17
C17H16N4S
(308.41)
10.40
(66.74)
72.14
(5.40)
5.10
(18.21)
17.71
(10.62)
C19H16N4O
(316.37)
–
–
–
−
(72.33)
76.41
(5.14)
5.77
(17.87)
17.82
C20H18N4
(314.39)
29
(77.73)
72.51
(5.73)
4.43
(17.97)
23.06
C22H16N6
(364.41)
32
215
(72.84)
68.87
(4.68)
5.17
(23.18)
21.13
C19H17N5O
(331.38)
35
178
(69.01)
(5.29)
(21.49)
Table 3 IR , 1H- and 13C-NMR of the new compounds.
Compd.
IR (cm-1)
1H and 13C-NMR (δ, ppm)
10
12
13
3226 (NH), 2215 (CN), 1717 (CO). 1.64-1.98 (m, 8H, 4CH2); 7.13-7.35 (m, 5H, Ar-H).
8.10 (s, 1H, NH).
3424-3345 (NH2), 3166 (NH), 1650 1.62-2.84 (m, 8H, 4CH2); 5.81 (s, 2H, NH2), 7.20-
(C=N).
7.44 (m, 5H, Ar-H), 13.71 (s, 1H, NH).
3266 (NH), 2215 (CN), 1723 (CO), 1.64-2.83 (m, 8H, 4CH2); 4.12 (s, H, NH); 7.21-
1346 (CS).
7.63 (m, 10H, Ar-H).
14
3424-3345 (NH2), 3266 (NH),
1346(CS).
1.64-2.82 (m, 8H, 4CH2); 2.14 (s, 2H, NH2); 4.13
(1s,1H, NH), 6.42-7.41 (m, 10H, Ar-H).
-----
15
16
2215 (CN), 1723, 1672 (2CO).
3408-3320 (NH2), 1672 (CO).
1.64-2.84 (m, 8H, 4CH2); 5.41 (s, 2H, NH2); 7.13-
7.52 (m, 10H, Ar-H).
19
3421-3307 (NH2), 3126 (NH), 1346
(CS).
-----
22a
3419-3303 (NH2), 3126 (NH), 1692 1.64-2.98 (m, 8H, 4CH2); 5.41 (s, 2H, NH2), 7.13-
(C=O). 7.35 (m, 5H, Ar-H); 8.12 (s, 1H, NH).
22b
3419-3303 (NH2), 3146 (NH), 1363 1.64-2.98 (m, 8H, 4CH2); 5.42 (s, 2H, NH2), 7.23-
(CS). 7.45 (m, 5H, Ar-H); 8.12 (s, 1H, NH).

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Molecules 2007, 12
Table 3. Cont.
IR (cm-1)
1H and 13C-NMR (δ, ppm)
Compd.
26
3419-3303 (NH2), 3146 (NH), 2215 1H: 1.64-2.96 (m, 8H, 4CH2); 5.41 (s, 2H, NH2),
(CN), 1707 (C=O).
7.14-7.30 (m, 5H, Ar-H); 8.01 (s, 1H, NH).
13C: 22.6, 23.5, 25.2, 31.5 (4CH2); 80.34 (C-CN);
113.6 (C3-quinoline); 115.7 (CN); 124.4 (C=C-N);
127.3, 127.3, 129.5, 129.5, 129.5, 136.4 (Ph), 147.6
(C-2-quinoline); 149.4 (C-4-quinoline), 156.2 (=C-
N=), 169.2 (C=O); 176.4 (=C-NH2).
29
32
3319-3322 (NH2), 2217(CN),
1661 (C=N).
1.64-2.88 (m, 8H, 4CH2); 2.56(s,3H,CH3),
4.21(s, 2H, NH2); 7.13-7.46 (m, 5H, Ar-H).
-----
3419-3303 (NH2), 3146 (NH),
2215, 2217 (CN).
35
3419-3303 (NH2), 2228 (CN),
1707 (C=O), 1631 (C=N).
1.61-2.85 (m, 8H, 4CH2), 2.15 (s, 2H, NH2), 2.25 (s,
2H, NH2), 7.21-7.45 (m, 5H, Ar-H).
X-ray crystallography [13]
X-ray quality crystals of the title compound 10 were obtained by slow crystallization from
dimethyl sulfoxide. Experimental data is summarized in Table 1. The data were collected with the
maXus computer programs on a Bruker Nonius instrument [14-18].
References
1. Lichitsky, B. V., Dudinov, A. A.; Krayushkin, M. M. Reaction of 3-aminocyclohex-2-en-1-ones
with arylidenemalononitriles. Arkivoc 2001, 73-79.
2. Chaczatrian, K.; Chaczatrian, G.; Danel, A.; Tomasik P. The synthesis of 4-aryl-1H-pyrazolo[3,4-
b]quinolines. Arkivoc 2001, 63-69.
3. Nithyadevi V.; Rajendran, S. P. An efficient synthesis of benzo[b][1,8]naphthyridine-3-carboxylic
acid. J. Heterocycl. Chem. 2006, 43, 755-758.
4. Stadlbauer, W.; Hojas, G. Synthesis of 4-Azido-3-diazo-3H-pyrazolo[3, 4-b]quinolines. J. Chem.
Soc. Perkin. Trans 1 2000, 3085-3087.
5. Elkholy, Y. M.; Morsy, M. A. Facial synthesis of 5,6,7,8-tetrahydropyrimido[4,5-b]quinoline
derivatives. Molecules 2006, 11, 890-903.
6. Vijayalakshmi, S.; Ragunath, L.; Rajendran, S. P. A new approach to the synthesis of
benzo[b][1,8]-naphthyridine-4(1H)ones. Heterocycl. Commun. 2001, 7, 177-182.
7. El-Sayed, O. A.; Aboul-Enein, H. Y. Synthesis and antimicrobial activity of novel
pyrazolo[3,4-b]quinoline derivatives. Arch. Pharm. (Weinheim) 2001, 334, 117-120.

372
Molecules 2007, 12
8. Wolin, R.; Wang, D., Kelly, J.; Afonso, A.; James, L.; Kirschmeier, P.; Mcphail, A. T. Synthesis
and evaluation of pyrazolo[3,4-b]quinoline ribofuranosides and their derivatives as inhibitors of
Oncogenic Ras. Bioorg. Med. Chem. Lett. 1996, 6, 195- 200.
9. Tsuzuki, Y.; Yomita, K.; Sato, Y. Synthesis and structure activity relationships of 3-substituted-
1,4-dihydro-1,8-naphthyridine as novel antitumor agents. Bioorg. Med. Chem. Lett. 2004, 14, 12-
16.
10. Mefetah, H.; Brouant, P.; Charbit, J.; Galy, A.M.; Barbe, J. Synthesis, trypanocidal activity and
DNA binding of new benzo[b][1,8]naphthyridine derivatives. Heterocycl. Commun. 1994, 1, 27-
35.
11. Antoine, M.; Barreau, M.; Descon, C.; Philippe, G.; Guy, P. Benzo[b][1,8]naphthyridine
derivatives, their preparation and pharmaceutical compositions as antimicrobial agents. US Pat.
6548506, 2003.
12. Shuka, H. K.; Desia, N. C.; Astik, R. R.; Thaker, K. A. The uses of phenylthiosemecarbazide in
heterocyclic syntheses. J. Indian Chem. Soc. 1984, 61, 168-175.
13. CCDC 632344 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
14. Mackay, S.; Gilmore, C. J.; Edwards, C.; Stewart, N.; Shankland, K. maXus Computer Program
for the Solution and Refinement of Crystal Structures; Bruker Nonius: Delft, The Netherlands and
Mac Science: Japan & The University of Glasgow, 1999.
15. Johnson, C. K. ORTEP--II. A FORTRAN Thermal--Ellipsoid Plot Program. Report ORNL-5138;
Oak Ridge National Laboratory: Oak Ridge, Tennessee, USA, 1976.
16. Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter, Jr., C. W.; Sweet, R. M., Eds.;
Academic Press: New York, 1997; Vol. 276, 307-326.
17. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla, M. C., Polidori, G.; Camalli,
M. Pi-halogen dimer interactions and the inclusion chemistry of new tetrahaloaryl host. J. Appl.
Cryst. 1994, 27, 435.
18. Waasmaier, D.; Kirfel, A. Data activities in crystallography, factor function for free atoms and
ions. Acta Cryst. 1995, A51, 416-431.
Sample availability: Available from the author.
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