Synthesis of some novel pyrazole-substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and cytotoxic activities

Article abstract of DOI:10.1002/jhet.848

This article focuses on the synthesis of new series of pyrazole-substituted 9-anilinoacridine derivatives 5a-m and 6a-l. The compounds were confirmed by physical and analytical data. The synthesized compounds when screened for in vitro antioxidant activity showed promising activity for many compounds. The selected compounds were screened for cytotoxic activity showed promising inhibition of HEp-2 cell line for the compounds 6c, 6e, and 6f.

Full text of DOI:10.1002/jhet.848

Month 2012
Synthesis of Some Novel Pyrazole-Substituted 9-Anilinoacridine
Derivatives and Evaluation for their Antioxidant and
Cytotoxic Activities
*
R. Kalirajan, V. Muralidharan, S. Jubie, B. Gowramma,
S. Gomathy, S. Sankar, and K. Elango
Department of Pharmaceutical Chemistry, JSS College of Pharmacy (Off Campus, JSS University, Mysore)
Ootacamund, Tamilnadu 643001, India
*
E-mail: rkalirajan@ymail.com or rkalirajan@jsscpooty.org
Received September 9, 2010
DOI 10.1002/jhet.848
Published online 00 March 2012 in Wiley Online Library (wileyonlinelibrary.com).
This article focuses on the synthesis of new series of pyrazole-substituted 9-anilinoacridine derivatives
5a–m and 6a–l. The compounds were confirmed by physical and analytical data. The synthesized com-
pounds when screened for in vitro antioxidant activity showed promising activity for many compounds.
The selected compounds were screened for cytotoxic activity showed promising inhibition of HEp-2 cell line
for the compounds 6c, 6e, and 6f.
J. Heterocyclic Chem., 00, 00 (2012).
INTRODUCTION
RESULTS AND DISCUSSION
Acridine derivatives are used in medicine and have
enormous potential as pharmaceutical agents due to their
biological activities such as antimicrobial [1], antioxidant
[2], anticancer [3], antimalarial [4], anti-inflammatory [5],
analgesic [6], antileishmanial [7], and antinociceptive [8],
acetyl cholinesterase inhibitors [9], and antiherpes [10]. The
chemical modification of 9-anilinoacridines such as the
introduction of different substitutions or heteroatoms has
allowed expansion of research on the structure–activity
relationship to afford new insight into molecular interac-
tions at the receptor level [11]. In fact, it is well
established that slight structural modification on 9-
anilinoacridine ring may bring various pharmacological
effects [12–18]. To look for some new compounds with
interesting biological properties, we have synthesized some
novel pyrazole-substituted 9-anilinoacridine derivatives.
In this study, the title compounds 5a–m and 6a–l
were prepared according to the procedure outlined in
Scheme 1. 9-Chloroacridine (2) was substituted with
4-aminoacetophenone gave 1-[4-(acridin-9-ylamino)phenyl]
ethanone (3). The compound 3 was then reacted with
corresponding aromatic aldehydes (Ar-CHO) in the presence
of NaOH in ethanol at room temperature gave chalcones
4a–n (yield more than 60%). Cyclization of 4a–n with
hydrazines (R-NH-NH2) in the presence of absolute
ethanol at reflux temperature afforded pyrazole-substituted
9-anilinoacridines 5a–m and 6a–l in good yields.
The chemical structure of the synthesized compounds
1
was elucidated by IR, H NMR, 13C NMR, and MS spec-
tral data. According to the IR spectral data, 4a–n showed
the C=O peaks at 1600–1700 cmÀ1 region, which are dis-
appeared for compounds 5a–m and 6a–l. The NH bands
© 2012 HeteroCorporation

R. Kalirajan, V. Muralidharan, S. Jubie, B. Gowramma, S. Gomathy, S. Sankar, and K. Elango
Vol 000
Scheme 1
of 5a–m were observed in the region 3300–3400 cmÀ1
.
experimental procedures [20]. The results, expressed as
In the 1H NMR spectra of 5a–m, the -NH proton of
pyrazole ring was observed as a broad singlet at about
13.00–13.85 ppm. But in 6a–l, it was not appeared
because of phenyl substitution. All other aromatic and
aliphatic protons of the compounds were observed at
the expected regions. 13C NMR of the compounds gave
prominent signals, which provide further evidence for
their structures. Mass spectra of all the synthesized
compounds showed M+/M+ + 1 peaks in agreement
with their molecular formulae.
The in vitro antioxidant activity of the newly synthesized
compounds 4a–n, 5a–m, and 6a–l was evaluated by DPPH
assay in accordance with the previously described experi-
mental procedures [19]. The results, expressed as IC50
values are reported in Table 1, suggested that all com-
pounds showed antioxidant activity but 5a,b,d,e,f,g,l,m
and 6a,b,c,d,e,f,i,j have potent antioxidant activity. The
compounds with potent antioxidant activity were screened
for their in vitro cytotoxicity.
CTC50 values are reported in Table 2, suggested that all
compounds showed a detectable cytotoxic activity but
compounds 6e and 6f are highly potent.
In conclusion, a series of novel pyrazole-substituted
9-anilinoacridines have been designed and synthesized.
The antioxidant and cytotoxic activities of the synthe-
sized compounds were evaluated. Among these com-
pounds, 6e and 6f showed good cytotoxic activity and
emerged as potential molecules for further development.
With this set of analogs, we are now in a position to
investigate the multiple biological activities of these
compounds.
EXPERIMENTAL
Melting points were determined on a Veego VMP-1 melt-
ing point apparatus and are uncorrected. IR spectra were
recorded on a Shimadzu 8400S FTIR spectrometer. 1H NMR
spectra and 13C NMR on Bruker AV III 500 MHz spectrom-
eter (500 MHz for 1H NMR spectra and 125 MHz for 13C
NMR) using TMS as an internal standard and CDCl3 as the
solvent. The chemical shifts are expressed in ppm (d). Mass
spectra were obtained on JOEL GCmate mass spectrometer.
Elemental analyses were determined by using Perkin–Elmer
The in vitro cytotoxicity of 5e, 5f, 5g, 5l, 5m, 6a, 6c, 6e,
6f, and 6i was evaluated by sulforhodamine-B (SRB) assay
on a human tumor cell lines, HEp-2 (laryngeal epithelial
carcinoma) in accordance with the previously described
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2012
Synthesis of Some Novel Pyrazole-Substituted 9-Anilinoacridine
Derivatives and Evaluation for their Antioxidant and Cytotoxic Activities
Table 1
Antioxidant activity of synthesized compounds by DPPH method.
IC50 valuesa
IC50 valuesa
IC50 valuesa
Compound
(mg/mL)
Compound
(mg/mL)
Compound
(mg/mL)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
2.69 Æ 0.05
5a
5b
5c
5d
5e
5f
5g
5h
5l
5m
–
20.50 Æ 1.32
19.25 Æ 0.85
97.80 Æ 6.39
09.62 Æ 0.55
11.80 Æ 0.73
14.87 Æ 0.12
14.75 Æ 0.77
198.00 Æ 2.07
13.92 Æ 0.20
7.06 Æ 0.25
–
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
–
–
10.80 Æ 0.51
29.00 Æ 0.83
12.00 Æ 0.41
30.75 Æ 1.19
12.37 Æ 1.28
7.15 Æ 0.31
156.00 Æ 1.67
107.25 Æ 2.66
21.50 Æ 2.32
28.50 Æ 0.95
46.75 Æ 2.01
83.00 Æ 2.24
–
–
–
–
–
–
–
–
Standard ascorbic acid
–
aAverage of four determinations. Values in bold represent potent antioxidant activity.
240C elemental analysis instrument. Reactions were carried
out and monitored by thin layer chromatography plates
(5 Â 20 cm) with 0.2 mm silica gel GF and the spots were
viewed in UV or iodine chamber.
saturated sodium carbonate solution and finally with water,
dried, and crystallized from ethanol. The yield of 9-
chloroacridine was 73%.
Procedure for the synthesis of 1-[4-(acridin-9-ylamino)
phenyl]ethanone (3). In a 250-mL round-bottomed flask, 4.06 g
(0.03 mol) of 4-aminoacetophenone was refluxed with 5.453 g
(0.0256 mol) of 9-chloroacridine in 80 mL of 2-butanol for 3 h.
After the reaction, the reaction mixture was allowed to cool to
room temperature, then it was poured into 150 mL of ice water.
The precipitate formed was filtered by suction, washed with
water, dried, and recrystallized from ethanol. The yield was 68%.
Procedure for the synthesis of 9-chloroacridine (2). A
mixture of 1.278 g (0.006 mol) of N-phenylanthranilic acid
and 19.781 g (0.131 mol) of phosphorous oxy chloride was
taken in a 250-mL round-bottomed flask and heated slowly
in a water bath at 85–90ꢀC for 15 min. It was observed
carefully that if the reaction becomes too violent, then the
flask was placed in a cold water bath for a moment (boiling
subsides). Then, the flask was immersed in an oil bath,
temperature was raised to 135–140ꢀC, and maintained under
reflux for 3 h. After the reaction, excess of phosphorus oxy
chloride was removed by the distillation from an oil bath at
140–150ꢀC under vacuum. After cooling to room temperature,
the reaction mixture was poured into a well-stirred mixture of
5.21 mL of concentrated ammonia and 13 g of crushed ice and
allowed to stand for 30 min to precipitate the solid. The
precipitate was filtered by suction, washed three times with
General procedure for the synthesis of chalcone deriva-
tives of 9-anilinoacridine (4a–n). Twenty-five milliliters of
10% sodium hydroxide and 25 mL of ethanol were taken in a
100 mL-flat-bottomed flask with a magnetic stirring bar and
was placed on the magnetic stirrer. To this solution, 0.0115 mol
of corresponding aldehyde and then 2.9952 g (0.0096 mol) of
1-[4-(acridin-9-ylamino)phenyl]ethanone (3) were added. The
solution was stirred at room temperature for 8 h. After the
reaction, 100 mL of water was added, the precipitate was
filtered, washed three times with 50 mL of water to remove
excess sodium hydroxide, dried, and recrystallized from ethanol.
Table 2
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(4-methoxyphenyl)
prop-2-en-1-one (4a). Yellow crystals, yield 79%, mp 179–181ꢀC.
IR (KBr, u, cmÀ1): 3273 (N-H), 3100–3000 (Ar C-H), 1626
(a,b-unsaturated C=O), 1607 and 1510 (Ar C=C), 1260 (C-N),
1168 (C-O), 748 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.01
(s, 1H, NH), 7.56 (d, 1H, CH), 7.90 (d, 1H, CH), 8.06–6.62
(m, 14H, Ar-H), 3.73 (s, 3H, OCH3). MS (m/z): 431 (M + 1).
Anal. Calcd for C29H22N2O2 (430): C, 80.91; H, 5.15; N, 6.51.
Found: C, 80.83; H, 5.23; N, 6.44.
Cytotoxicity study of some selected compound by SRB assay.
CTC50 valuesa
Sl. no.
Compound
in (mg/mL)
1
2
3
4
5
6
7
8
9
10
5e
5f
5g
5l
5m
6a
6c
6e
6f
90.33 Æ 1.66
60.14 Æ 0.33
125.24 Æ 1.10
115.08 Æ 0.95
50.32 Æ 2.03
>250
40.53 Æ 0.86
34.56 Æ 1.53
35.79 Æ 0.39
62.45 Æ 0.62
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-phenylprop-2-en-
1-one (4b). Yellow crystals, yield 78%, mp 180–182ꢀC. IR
(KBr, u, cmÀ1): 3269 (N-H), 3057–3000 (Ar C-H), 1647
(a,b-unsaturated C=O), 1604 and 1516 (Ar C=C), 1226 (C-N),
759 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.02 (s, 1H, NH),
8.06–6.62 (m, 16H, Ar-H), 7.56 (d, 1H, CH), 7.90 (d, 1H, CH).
6i
aAverage of three determinations. Values in bold represent more potent.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Kalirajan, V. Muralidharan, S. Jubie, B. Gowramma, S. Gomathy, S. Sankar, and K. Elango
Vol 000
MS (m/z): 401.1 (M+ + 1). Anal. Calcd for C28H20N2O
(400.16): C, 83.97; H, 5.04; N, 7.01. Found: C, 83.84; H,
5.12; N, 7.13.
IR (KBr, u, cmÀ1): 3290 (N-H), 3100–3000 (Ar C-H), 1627
(a,b-unsaturated C=O), 1577 and 1498 (Ar C=C), 1280 (C-N),
748 (Ar C-H). 1H NMR (CDCl3) d ppm: 3.98 (s, 1H, NH),
7.58 (d, 1H, CH), 7.89 (d, 1H, CH), 8.1–6.63 (m, 15H, Ar-H).
MS (m/z): 402.15 (M+ + 1). Anal. Calcd for C27H19N3O
(401.4): C, 80.80; H, 4.77; N, 10.48. Found: C, 80.67; H,
4.60; N, 10.28.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(3-nitrophenyl)prop-
2-en-1-one (4j). Orange crystals, yield 83%, mp 188–190ꢀC.
IR (KBr, u, cmÀ1): 3034 (N-H), 3100–3000 (Ar C-H), 1626
(a,b-unsaturated C=O), 1577 and 1498 (Ar C=C), 1529 and
1348 (NO2), 1280 (C-N), 748 (Ar C-H). 1H NMR (CDCl3)
d ppm: 4.08 (s, 1H, NH), 7.81 (d, 1H, CH), 8.02 (d, 1H,
CH), 8.2–6.64 (m, 15H, Ar-H). MS (m/z): 445.14 (M+).
Anal. Calcd for C28H19N3O3 (445.5): C, 75.50; H, 4.30; N,
9.42. Found: C, 75.26; H, 4.52; N, 9.51.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(3-hydroxy-4-
methoxyphenyl)prop-2-en-1-one (4k). Yellow crystals, yield
58%, mp 206–208ꢀC. IR (KBr, u, cmÀ1): 3560 (N-H), 3302
(O-H), 3100–3000 (Ar C-H), 1654 (a,b-unsaturated C=O),
1599 and 1496 (Ar C=C), 1278 and 1107 (C-O), 1178 (C-N),
763 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.38 (s, 1H, NH), 3.78
(s, 3H, CH3), 4.88 (s, 1H, OH), 7.58 (d, 1H, CH), 7.88 (d, 1H,
CH), 8.2–6.66 (m, 14H, Ar-H). MS (m/z): 447.05 (M+ + 1).
Anal. Calcd for C29H22N2O3 (446.5): C, 78.11; H, 4.95; N,
6.28. Found: C, 78.22; H, 4.85; N, 6.31.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(2-hydroxyphenyl)
prop-2-en-1-one (4c). Yellow crystals, yield 65%, mp 209–211ꢀC.
IR (KBr, u, cmÀ1): 3560 (N-H), 3302 (O-H), 3100–3000
(Ar C-H), 1654 (a,b-unsaturated C=O), 1627 and 1516 (Ar C=C),
1280 (C-N), 1151 (C-O), 748 (Ar C-H). 1H NMR (CDCl3)
d ppm: 4.12 (s, 1H, NH), 5.08 (s, 1H, OH), 7.56 (d, 1H, CH),
7.90 (d, 1H, CH), 8.03–6.65 (m, 14H, Ar-H). MS (m/z): 416.2
(M+). Anal. Calcd for C28H20N2O2 (416.15): C, 80.73; H, 4.85;
N, 6.72. Found: C, 80.62; H, 4.91; N, 6.66.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(furan-2-yl)prop-2-
en-1-one (4d). Yellow crystals, yield 66%, mp 179–181ꢀC.
IR (KBr, u, cmÀ1): 3300 (N-H), 3057–3034 (Ar C-H), 1651
(a,b-unsaturated C=O), 1606 and 1512 (Ar C=C), 1230 (C-N),
1176 (C-O), 759 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.04
(s, 1H, NH), 7.58 (d, 1H, CH), 7.91 (d, 1H, CH), 8.04–6.64
(m, 14H, Ar-H). MS (m/z): 391.14 (M+ + 1). Anal. Calcd
for C26H18N2O2 (390.4): C, 79.97; H, 4.64; N, 7.17. Found:
C, 79.88; H, 4.53; N, 7.25.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(4-hydroxyphenyl)
prop-2-en-1-one (4e). Yellow crystals, yield 56%, mp 208–210ꢀC.
IR (KBr, u, cmÀ1): 3302 (N-H), 3238 (O-H), 3059–3034 (Ar C-H),
1626 (a,b-unsaturated C=O), 1626 and 1527 (Ar C=C), 1280
(C-N), 1151 (C-O), 748 (Ar-C-H). 1H NMR (CDCl3) d ppm:
4.02 (s, 1H, NH), 5.06 (s, 1H, OH), 7.57 (d, 1H, CH), 8.02–6.62
(m, 14H, Ar-H). MS (m/z): 416.1 (M+). Anal. Calcd for
C28H20N2O2 (416.15): C, 80.74; H, 4.85; N, 6.75. Found: C,
80.53; H, 4.97; N, 6.64.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(4-chlorophenyl)
prop-2-en-1-one (4l). Yellow crystals, yield 64%, mp 188–190ꢀC.
IR (KBr, u, cmÀ1): 3302 (N-H), 3100–3000 (Ar C-H), 1651
(a,b-unsaturated C=O), 1606 and 1518 (Ar C=C), 1267 (C-N),
748 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.14 (s, 1H, NH),
7.56 (d, 1H, CH), 7.91 (d, 1H, CH), 8.2–6.60 (m, Ar-H).
MS (m/z): 435.12 (M+). Anal. Calcd for C28H19ClN2O (434.2):
C, 77.37; H, 4.42; N, 6.44. Found: C, 77.25; H, 4.29; Cl, 8.15;
N, 6.62.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(2-chlorophenyl)
prop-2-en-1-one (4m). Cherry red crystals, yield 62%, mp
190–192ꢀC. IR (KBr, u, cmÀ1): 3279 (N-H), 3109–2999
(Ar C-H), 1647 (a,b-unsaturated C=O), 1591 and 1496 (Ar C=C),
1273 (C-N), 746 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.04
(s, 1H, NH), 8.13 (d, 1H, CH), 7.35 (d, 1H, CH), 8.1–6.65
(m, 14H, Ar-H). MS (m/z): 435.16 (M+ + 1). Anal. Calcd
for C28H19ClN2O (434.1): C, 77.35; H, 4.42; 2 N, 6.44.
Found: C, 77.59; H, 4.20; N, 6.25.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(4-(dimethylamino)
phenyl)prop-2-en-1-one (4f). Orange crystals, yield 65%, mp
165–167ꢀC. IR (KBr, u, cmÀ1): 3313 (N-H), 3099–2999 (Ar C-H),
1654 (a,b-unsaturated C=O), 1604 and 1500 (Ar-C=C), 1261
(C-N), 750 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.03 (s, 1H,
NH), 2.83 (s, 6H, CH3), 7.54 (d, 1H, CH), 8.02–6.62 (m, 15H,
Ar-H). MS (m/z): 444.20 (M+ + 1). Anal. Calcd for C30H25N3O
(443.5): C, 81.26; H, 5.65; N, 9.43. Found: C, 81.09; H, 5.75;
N, 9.30.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(2,4-dichlorophenyl)
prop-2-en-1-one (4g). Orange crystals, yield 75%, mp 228–230ꢀC.
IR (KBr, u, cmÀ1): 3294 (N-H), 3100–3000 (Ar C-H), 1649
(a,b-unsaturated C=O), 1606 and 1518 (Ar C=C), 1257 (C-N),
756 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.1 (s, 1H, NH),
7.34 (d, 1H, CH), 8.17 (d, 1H, CH), 8.02–6.62 (m, 14H, Ar-H).
MS (m/z): 470.08 (M+ + 1). Anal. Calcd for C28H18Cl2N2O
(469.3): C, 71.64; H, 3.89; N, 5.97. Found: C, 71.72; H,
3.77; N, 5.81.
(2E,4E)-1-(4-(Acridin-9-ylamino)phenyl)-5-phenylpenta-2,4-
dien-1-one (4n). Yellow crystals, yield 58%, mp 218–220ꢀC.
IR (KBr, u, cmÀ1): 3234 (N-H), 3100–3000 (Ar C-H), 1633
(a,b-unsaturated C=O), 1600 and 1514 (Ar C=C), 1254 (C-N),
761 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.10 (s, 1H, NH),
7.23 (d, 1H, CH), 7.77 (d, 1H, CH), 8.05–6.66 (m, 16H, Ar-H).
MS (m/z): 427.1 (M+ + 1). Anal. Calcd for C30H22N2O
(426.2): C, 84.50; H, 5.18; N, 6.58. Found: C, 84.72; H,
5.03; N, 6.42.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(4-(benzyloxy)-3-
methoxyphenyl)prop-2-en-1-one (4h). Orange crystals, yield
73%, mp 77–79ꢀC. IR (KBr, u, cmÀ1): 3304 (N-H), 3061–3012
(Ar C-H), 1674 (a,b-unsaturated C=O), 1627 and 1506 (Ar C=C),
1265 and 1134 (C-O), 1236 (C-N), 748 (Ar C-H). 1H NMR
(CDCl3) d ppm: 4.08 (s, 1H, NH), 3.78 (s, 3H, CH3), 5.18
(s, 2H, CH2), 7.54 (d, 1H, CH), 7.91 (d, 1H, CH), 8.03–6.65
(m, 18H, Ar-H). MS (m/z): 537.21 (M+ + 1). Anal. Calcd
for C36H28N2O3 (536.6): C, 80.55; H, 5.25; N, 5.22. Found:
C, 80.69; H, 5.35; N, 5.29.
Synthesis of pyrazole-substituted 9-anilinoacridines
(5a–m). A solution of 0.0025 mol of the corresponding
chalcones 4a–n in 20 mL of absolute ethanol and 0.2503 g
(0.005 mol) of hydrazine hydrate (99%) were taken in a
100-mL round-bottomed flask and refluxed for 6 h. After the
reaction, the solvent was removed by vacuum distillation,
then the residue obtained was washed with water, dried, and
recrystallized from ethanol.
(E)-1-(4-(Acridin-9-ylamino)phenyl)-3-(pyridin-3-yl)prop-2-
en-1-one (4i). Orange crystals, yield 61%, mp 124–126ꢀC.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2012
Synthesis of Some Novel Pyrazole-Substituted 9-Anilinoacridine
Derivatives and Evaluation for their Antioxidant and Cytotoxic Activities
N-(4-(5-(4-Methoxyphenyl)-1H-pyrazol-3-yl)phenyl)acridin-
9-amine (5a). Orange crystals, yield 55%, mp 97–99ꢀC. IR
(KBr, u, cmÀ1): 3306 (N-H), 3100–2999 (Ar C-H), 1593 and
1514 (Ar C=C), 1263 and 1151 (C-O), 1246 (C-N), 750 (Ar
C-H). 1H NMR (CDCl3) d ppm: 13.01 (s, 1H, pyrazole,NH),
4.18 (s, 1H, NH), 7.80–6.65 (m, 17H, Ar-H), 3.80 (s, 3H,
OCH3). 13C NMR: 126.7, 127.45, 130.89, 126.02, 127.03,
125.75, 151.74, 117.42, 134.93, 133.42, 120.35, 132.75,
123.64, 128.27, 125.16, 121.34, 123.17, 140.21, 113.71,
135.11, 129.13, 127.51, 129.13, 159.16, 121.42, 127.51,
55.32. MS EI (m/z): 441.67 (M+, 20%), 426.84 (24%),
397.14 (48%), 306.88 (100%), 289.93 (60%), 263.11 (64%),
217.32 (40%), 190.44 (38%), 175.51 (50%). Anal. Calcd for
C29H22N4O: C, 78.71; H, 5.01; N, 12.66; O, 3.62. Found: C,
78.57; H, 5.23; N, 12.54.
N-(4-(5-Phenyl-1H-pyrazol-3-yl)phenyl)acridin-9-amine
(5b). Orange crystals, yield 80%, mp 110–112ꢀC. IR (KBr,
u, cmÀ1): 3269 (N-H), 3100–3000 (Ar C-H), 1591 and 1489
(Ar C=C), 1263 (C-N), 754 (Ar C-H). 1H NMR (CDCl3) d
ppm: 13.05 (s, 1H, pyrazole,NH), 3.96 (s, 1H, NH), 7.80–6.65
(m, 18H, Ar-H). 13C NMR: 127.59, 127.73, 130.54, 127.52,
127.46, 130.51, 127.66, 151.48, 117.36, 130.88, 130.74,
120.35, 130.65, 126.14, 128.80, 126.36, 128.84, 125.79,
142.89, 114.81, 133.45, 128.83, 128.51, 128.73, 125.16,
123.85, 128.51. MS EI (m/z): 411.59 (M+, 100%), 391.17
(24%), 382.40 (16%), 308.90 (30%), 291.94 (22%), 266.08
(32%), 204.06 (16%), 177.54 (12%). Anal. Calcd for C28H20N4
(412.19): C, 81.55; H, 4.89; N, 13.59. Found: C, 81.32; H,
4.91; N, 13.541.
2-(3-(4-(Acridin-9-ylamino)phenyl)-1H-pyrazol-5-yl)phenol
(5c). Yellow crystals, yield 63%, mp 203–205ꢀC. IR (KBr, u,
cmÀ1): 3313 (N-H), 3100–2995 (Ar C-H), 1604 and 1498 (Ar
C=C), 1261 (C-N), 1147 (C-O), 750 (Ar C-H). 1H NMR
(CDCl3) d ppm: 13.11 (s, 1H, pyrazole,NH), 5.04 (s, 1H,
OH), 4.09 (s, 1H, NH), 7.77–6.83 (m, 17H, Ar-H). 13C
NMR: 125.71, 127.07, 130.02, 125.71, 125.73, 130.08,
126.76, 124.62, 151.74, 116.65, 130.90, 130.60, 120.35,
130.62, 121.46, 128.24, 124.62, 128.22, 121.34, 147.35,
115.49, 135.11, 129.13, 159.16, 129.13, 120.36, 121.35,
128.21. MS EI (m/z): 427.52 (M+, 20%), 356.16 (10%),
318.84 (56%), 309.87 (100%), 294.86 (68%), 266.10 (74%),
177.50 (70%). Anal. Calcd for C28H20N4O (428.16): C,
78.45; H, 4.73; N, 13.08. Found: C, 78.53; H, 4.47; N, 13.23.
N-(4-(5-(Furan-2-yl)-1H-pyrazol-3-yl)phenyl)acridin-9-
amine (5d). Brownish orange crystals, yield 78%, mp 108–110ꢀC.
IR (KBr, u, cmÀ1): 3100–3000 (Ar C-H), 1591 and 1485 (Ar
C=C), 1263 (C-N), 1151 (C-O), 752 (Ar C-H). 1H NMR
(CDCl3) d ppm: 13.02 (s, 1H, pyrazole,NH), 4.09 (s, 1H,
NH), 7.85–6.22 (m, 16H, Ar-H). 13C NMR: 125.64, 127.50,
130.41, 125.10, 125.13, 130.41, 126.99, 123.65, 152.15, 105.93,
130.68, 130.41, 110.27, 130.68, 120.35, 130.68, 121.35, 128.21,
117.25, 147.42, 105.93, 142.24, 116.60, 154.89, 129.12, 127.56,
114.71. MS EI (m/z): 399.14 (M+ - 3, 100%), 387.30 (20%),
308.84 (24%), 291.91 (32%), 266.04 (28%), 177.51 (24%). Anal.
Calcd for C26H18N4O (402.15): C, 77.57; H, 4.53; N, 13.92.
Found: C, 77.50; H, 4.48; N, 13.81.
7.86–6.79 (m, 17H, Ar-H). 13C NMR: 125.71, 127.07,
130.02, 124.62, 124.63, 130.02, 126.74, 121.45, 152.27,
116.67, 133.45, 130.85, 120.37, 130.60, 120.35, 128.22,
121.34, 128.22, 127.07, 147.75, 115.49, 135.11, 129.10,
127.07, 129.10, 159.11, 121.47, 127.07. MS EI (m/z):
427.12 (M+, 8%), 400.15 (10%), 377.41 (12%), 309.67
(20%), 232.83 (16%), 192.44 (24%), 177.46 (44%). Anal.
Calcd for C28H20N4O (428.16): C, 78.51; H, 4.71; N, 13.18.
Found: C, 78.56; H, 4.64; N, 13.23.
N-(4-(5-(4-(Dimethylamino)phenyl)-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (5f). Brown crystals, yield 62%, mp 138–140ꢀC.
IR (KBr, u, cmÀ1): 3313 (N-H), 3100–3000 (Ar C-H), 1599
and 1473 (Ar C=C), 1261 (C-N), 750 (Ar C-H). 1H NMR
(CDCl3) d ppm: 13.12 (s, 1H, pyrazole,NH), 4.13 (s, 1H,
NH), 3.04 (s, 6H, 2CH3), 7.85–6.67 (m, 17H, Ar-H). 13C
NMR: 122.10, 127.49, 130.89, 117.35, 117.34, 130.64,
126.78, 117.28, 152.13, 112.08, 130.85, 130.64, 113.71,
130.85, 111.24, 129.55, 114.76, 147.51, 111.96, 133.42,
129.89, 128.26, 129.73, 160.81, 114.50, 128.26, 40.22,
40.31. MS EI (m/z): 454.44 (25%), 387.87 (12%), 355.46
(20%), 322.12 (56%), 308.76 (36%), 284.70 (32%), 217.80
(26%), 198.95 (32%), 176.32 (22%). Anal. Calcd for
C30H25N5 (455.21): C, 79.12; H, 5.55; N, 15.39. Found: C,
79.25; H, 5.42; N, 15.12.
N-(4-(5-(2,4-Dichlorophenyl)-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (5g). Orange crystals, yield 64%, mp 110–112ꢀC.
IR (KBr, u, cmÀ1): 3282 (C-N), 3100–3000 (Ar C-H), 1606
and 1515 (Ar C=C), 1263 (C-N), 752 (Ar C-H). 1H NMR
(CDCl3) d ppm: 13.03 (s, 1H, pyrazole,NH), 4.07 (s, 1H,
NH), 7.68–6.66 (m, 16H, Ar-H). 13C NMR: 128.43, 129.30,
130.40, 125.15, 128.33, 131.75, 129.01, 127.58, 151.53,
117.42, 138.73, 133.67, 120.27, 133.36, 127.46, 130.60,
127.53, 130.61, 125.79, 147.44, 114.78, 138.90, 130.80,
138.90, 130.80, 138.73, 123.78, 130.40. MS EI (m/z):
480.26 (M+, 8%), 464.18 (32%), 455.64 (36%), 414.84
(28%), 333.68 (28%), 307.89 (100%), 290.93 (56%), 265.07
(62%), 168.47 (32%). Anal. Calcd for C28H18Cl2N4 (480.1):
C, 69.89; H, 3.79; N, 11.67. Found: C, 69.74; H, 3.65; N,
11.82.
N-(4-(5-(4-(Benzyloxy)-3-methoxyphenyl)-1H-pyrazol-3-yl)
phenyl)acridin-9-amine (5h). Brown crystals, yield 54%, mp
140–142ꢀC. IR (KBr, u, cmÀ1): 3348 (N-H), 3100–3032 (Ar
C-H), 1620 and 1508 (Ar C=C), 1273 (C-N), 1259 and
1139 (C-O), 748 (Ar C-H). 1H NMR (CDCl3) d ppm: 13.63
(s, 1H, pyrazole,NH), 4.12 (s, 1H, NH), 3.78 (s, 3H, CH3),
8.18–6.56 (m, 20H, Ar-H). 13C NMR: 129.13, 129.70,
126.28, 124.55, 114.75, 149.3, 114.93, 129.18, 148.33,
116.42, 143.21, 116.48, 128.27, 148.56, 128.46, 126.60,
123.24, 148.71, 100.05, 148.64, 112.28, 150.30, 120.83,
115.90, 149.80, 56.24, 71.38, 141.25, 127.26, 129.21,
127.56. MS EI (m/z): 548.12 (M+, 100%). Anal. Calcd for
C36H28N4O2 (548.23): C, 78.83; H, 5.16; N, 10.31. Found:
C, 78.59; H, 5.24; N, 10.09.
N-(4-(5-(4-Chlorophenyl)-1H-pyrazol-3-yl)phenyl)acridin-9-
amine (5l). Yellow crystals, yield 55%, mp 198–200ꢀC. IR
(KBr, u, cmÀ1): 3379 (N-H), 3061–3001 (Ar C-H), 1620 and
1
4-(3-(4-(Acridin-9-ylamino)phenyl)-1H-pyrazol-5-yl)phenol
(5e). Brownish orange crystals, yield 61%, mp 152–154ꢀC.
IR (KBr, u, cmÀ1): 3313 (N-H), 3194 (C-O), 3100–2995 (Ar
C-H), 1604 and 1523 (Ar C=C), 1276 (C-N), 1261 and
1147 (C-O), 750 (Ar C-H). 1H NMR (CDCl3) d ppm: 13.23
(s, 1H, pyrazole,NH), 3.97 (s, 1H, NH), 5.62 (s, 1H, OH),
1518 (Ar C=C), 1263 (C-N), 750 (Ar C-H). H NMR (CDCl3)
d ppm: 13.79 (s, 1H, pyrazole,NH), 4.08 (s, 1H, NH), 8.08–6.45
(m, 16H, Ar-H). 13C NMR: 129.12, 129.63, 126.32, 124.63,
114.64, 149.65, 114.83, 126.62, 148.37, 116.84, 143.16, 116.48,
128.33, 148.78, 128.32, 126.53, 123.17, 148.83, 99.65, 148.76,
132.12, 148.30, 131.23, 128.86, 129.45, 134.32. MS EI (m/z):
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Kalirajan, V. Muralidharan, S. Jubie, B. Gowramma, S. Gomathy, S. Sankar, and K. Elango
Vol 000
1
446.15 (M+). Anal. Calcd for C28H19ClN4 (446.2): C, 75.27; H,
4.21; N, 12.52. Found: C, 75.13; H, 4.12; N, 12.62.
(Ar C=C), 1273 (C-N), 1220 and 1165 (C-O), 754 (Ar C-H). H
NMR (CDCl3) d ppm: 4.12 (s, 1H, NH), 8.03–6.31 (m, 20H,
Ar-H). 13C NMR: 129.21, 129.72, 126.33, 124.53, 114.69,
149.65, 114.65, 148.42, 126.52, 126.63, 129.66, 129.16,
116.82, 128.26, 123.18, 128.35, 152.74, 107.15, 152.57,
107.08, 127.06, 157.61, 107.32, 105.03, 142.93, 120.24,
129.35, 129.46, 126.25, 139.72. MS (m/z): 479.68 (M+ + 1).
Anal. Calcd for C32H22N4O (478.2): C, 80.42; H, 4.68; N,
11.73. Found: C, 80.14; H, 4.79; N, 11.58.
4-(3-(4-(Acridin-9-ylamino)phenyl)-1-phenyl-1H-pyrazol-5-yl)
phenol (6e). Brick red crystals, yield 63%, mp 295–297ꢀC. IR
(KBr, u, cmÀ1): 3250 (N-H), 3090 (O-H), 3070–3018 (Ar C-H),
1589 and 1506 (Ar C=C), 1273 (C-N), 1251 (C-O), 750 (Ar
N-(4-(5-(2-Chlorophenyl)-1H-pyrazol-3-yl)phenyl)acridin-9-
amine (5m). Dark brown crystals, yield 84%, mp 89–91ꢀC.
IR (KBr, u, cmÀ1): 3057–3030 (Ar C-H), 1608 and 1518 (Ar
C=C), 1263 (C-N), 752 (Ar C-H). 1H NMR (CDCl3) d ppm:
13.83 (s, 1H, pyrazole,NH), 4.12 (s, 1H, NH), 8.10–6.35 (m,
16H, Ar-H). 13C NMR: 129.17, 129.76, 126.37, 124.57,
114.74, 149.72, 114.79, 126.34, 148.74, 116.77, 143.12,
116.74, 128.28, 148.82, 128.36, 123.23, 126.7, 148.75,
99.81, 148.82, 130.02, 148.76, 132.31, 128.92, 129.52,
130.26. MS EI (m/z): 446.21 (M+). Anal. Calcd for
C28H19ClN4 (446.13): C, 75.28; H, 4.18; N, 12.57. Found:
C, 75.68; H, 4.04; N, 12.38.
1
C-H). H NMR (CDCl3) d ppm: 4.02 (s, 1H, NH), 5.08 (s, 1H,
OH), 8.03–6.48 (m, 20H, Ar-H). 13C NMR: 129.07, 129.59,
126.25, 124.38, 114.92, 149.25, 114.65, 148.73, 126.32, 126.43,
129.59, 129.06, 143.22, 116.68, 128.33, 123.21, 128.42, 153.66,
106.04, 144.48, 128.88, 116.37, 158.44, 116.41, 128.79, 120.23,
120.28, 126.38, 129.43, 139.67. MS (m/z): 505.32 (M+ + 1).
Anal. Calcd for C34H24N4O (504.2): C, 80.95; H, 4.73; N, 11.12.
Found: C, 80.68; H, 4.91; N, 11.24.
Synthesis of pyrazole-substituted 9-anilinoacridines
(6a–l). A solution of 0.0125 mol of the corresponding
chalcones 4a–n in 20 mL of absolute ethanol and 0.24 g
(0.0016 mol) of phenylhydrazine hydrochloride were taken
in a 100-mL round-bottomed flask and refluxed for 6 h.
After the reaction, the solvent was removed by vacuum
distillation, then the residue obtained was washed with
water and dried.
N-(4-(5-(4-(Dimethylamino)phenyl)-1-phenyl-1H-pyrazol-3-yl)
phenyl)acridin-9-amine (6f). Brick red crystals, yield 68%, mp
284–286ꢀC. IR (KBr, u, cmÀ1): 3254 (N-H), 3086–3000 (Ar C-H),
1589 and 1506 (Ar C=C), 1273 (C-N), 1251 and 1163 (C-O), 750
N-(4-(5-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (6a). Brick red crystals, yield 70%, mp
280–282ꢀC. IR (KBr, u, cmÀ1): 3250 (N-H), 3091–2953 (Ar
C-H), 1589 and 1496 (Ar C=C), 1273 (C-N), 1251 and 1165
(C-O), 750 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.05 (s, 1H,
NH), 8.06–6.35 (m, 21H, Ar-H), 3.78 (s, 3H, OCH3). 13C
NMR: 129.13, 129.75, 126.28, 128.89, 126.22, 127.03, 129.65,
125.75, 153.68, 114.72, 129.93, 130.12, 117.15, 128.25,
123.14, 128.32, 120.16, 129. 4, 120.17, 114.75, 160.73,
114.71, 125.11, 144.13, 139.51, 126.33, 129.06, 127.51, 55.83.
MS (m/z): 519.11 (M+). Anal. Calcd for C35H26N4O (518.2):
C, 81.16; H, 5.07; N, 10.83. Found: C, 81.19; H, 5.24; N, 10.65.
1
(Ar C-H). H NMR (CDCl3) d ppm: 4.11 (s, 1H, NH), 8.02–6.55
(m, 21H, Ar-H). 13C NMR: 129.11, 129.81, 126.34, 124.53,
114.69, 148.28, 114.73, 149.75, 126.28, 126.23, 129.71, 129.21,
143.13, 116.91, 128.38, 123.14, 128.37, 153.74, 106.24, 144.47,
122.63, 128.43, 114.76, 149.49, 114.41, 128.36, 120.28, 120.21,
126.31, 129.29, 40.27, 139.67, 40.25. MS (m/z): 532.27 (M+ + 1).
Anal. Calcd for C36H29N5 (531.25): C, 81.37; H, 5.53; N, 13.27.
Found: C, 81.05; H, 5.71; N, 13.46.
N-(4-(5-(2,4-Dichlorophenyl)-1-phenyl-1H-pyrazol-3-yl)
phenyl)acridin-9-amine (6g). Orange crystals, yield 60%, mp
230–232ꢀC. IR (KBr, u, cmÀ1): 3335 (N-H), 3100–3000 (Ar C-H),
N-(4-(1,5-Diphenyl-1H-pyrazol-3-yl)phenyl)acridin-9-amine
(6b). Brownish black crystals, yield 64%, mp 205–207ꢀC. IR
(KBr, u, cmÀ1): 3100–3000 (Ar C-H), 1600 and 1496 (Ar
C=C), 1273 (C-N), 750 (Ar C-H). 1H NMR (CDCl3) d ppm:
4.11 (s, 1H, NH), 8.02–6.51 (m, 22H, Ar-H). 13C NMR:
129.18, 129.64, 126.28, 124.52, 114.73, 149.25, 114.68,
148.32, 126.38, 126.33, 129.68, 129.15, 116.76, 128.43,
123.16, 128.28, 153.64, 106.08, 144.52, 127.48, 127.48,
133.16, 120.18, 129.43, 120.12, 129.73, 129.5, 126.29. MS
(m/z): 489.28 (M+ + 1). Anal. Calcd for C34H24N4 (488.2):
C, 83.68; H, 4.89; N, 11.51. Found: C, 83.39; H, 4.63; N,
11.25.
1
1583 and 1506 (Ar C=C), 1259 (C-N), 750 (Ar C-H). H NMR
(CDCl3) d ppm: 3.98 (s, 1H, NH), 8.06–6.47 (m, 20H, Ar-H).
13C NMR: 129.22, 129.74, 126.28, 124.61, 114.78, 148.93,
114.69, 148.34, 126.39, 126.42, 129.67, 129.18, 143.33, 116.86,
128.41, 123.08, 128.28, 153.69, 106.24, 144.47, 128.13, 133.67,
130.92, 135.67, 127.56, 130.36, 120.31, 120.25, 126.36, 129.35.
MS (m/z): 557.22 (M+ + 1). Anal. Calcd for C34H22Cl2N4
(556.1): C, 73.35; H, 3.92; N, 10.05. Found: C, 73.43; H, 3.74;
N, 10. 21.
N-(4-(5-(4-(Benzyloxy)-3-methoxyphenyl)-1-phenyl-1H-
pyrazole-3-yl)phenyl)acridin-9-amine (6h). Yellow crystals, yield
61%, mp 136–138ꢀC. IR (KBr, u, cmÀ1): 3300 (N-H), 3041–2993
(Ar C-H), 1600 and 1508 (Ar C=C), 1263 (C-N), 746 (Ar C-H).
1H NMR (CDCl3) d ppm: 3.67 (s, 1H, NH), 5.18 (s, 2H, CH2),
8.12–6.50 (m, 25H, Ar-H). 13C NMR: 129.12, 129.63, 126.22,
124.54, 114.65, 148.88, 114.71, 148.26, 126.25, 126.32, 129.58,
129.09, 143.13, 116.59, 128.29, 123.21, 128.21, 153.81, 106.08,
144.52, 112.18, 150.24, 130.92, 149.67, 115.56, 120.77, 120.33,
120.27, 126.31, 129.42, 56.34, 71.28, 127.35, 141.38, 129.03. MS
(m/z): 625.25 (M+ + 1). Anal. Calcd for C42H32N4O2 (624.15): C,
80.75; H, 5.16; N, 8.97; O, 5.12. Found: C, 80.53; H, 5.41; N, 8.72.
N-(4-(1-Phenyl-5-(pyridin-3-yl)-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (6i). Black crystals, yield 57%, mp 265–267ꢀC.
IR (KBr, u, cmÀ1): 3400 (N-H), 3030–3018 (Ar C-H), 1599 and
2-(3-(4-(Acridin-9-ylamino)phenyl)-1-phenyl-1H-pyrazol-5-yl)
phenol (6c). Brick red crystals, yield 71%, mp 290–292ꢀC. IR
(KBr, u, cmÀ1): 3400 (N-H), 3250 (O-H), 3088–3018 (Ar C-H),
1589 and 1506 (Ar C=C), 1273 (C-N), 1251 (C-O), 750 (Ar
1
C-H). H NMR (CDCl3) d ppm: 4.10 (s, 1H, NH), 5.08 (s, 1H,
OH), 8.02–6.45 (m, 21H, Ar-H). 13C NMR: 129.12, 129.74,
126.31, 124.62, 114.83, 149.65, 114.78, 148.36, 126.78, 126.73,
129.72, 129.12, 116.66, 128.33, 123.21, 128.28, 153.72, 106.02,
144.52, 120.58, 155.41, 116.36, 120.58, 129.93, 120.22, 129.38,
129.42, 126.34, 139.65. MS (m/z): 505.31 (M+ + 1). Anal. Calcd
for C34H24N4O (505.3): C, 80.83; H, 4.82; N, 11.15. Found: C,
80.17; H, 4.58; N, 11.02.
N-(4-(5-(Furan-2-yl)-1-phenyl-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (6d). Orange crystals, yield 56%, mp 298–300ꢀC.
IR (KBr, u, cmÀ1): 3323 (N-H), 3090–3022 (Ar C-H), 1599 and 1489
1
1494 (Ar C=C), 1273 (C-N), 748 (Ar C-H). H NMR (CDCl3)
d ppm: 4.15 (s, 1H, NH), 8.86–6.35 (m, 21H, Ar-H). 13C
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2012
Synthesis of Some Novel Pyrazole-Substituted 9-Anilinoacridine
Derivatives and Evaluation for their Antioxidant and Cytotoxic Activities
NMR: 129.07, 129.64, 126.23, 124.54, 114.69, 148.63, 114.75,
148.27, 126.28, 126.34, 129.62, 129.12, 143.13, 116.69,
128.24, 123.12, 128.41, 152.49, 107.08, 127.28, 134.16,
133.21, 124.12, 148.09, 139.64, 120.28, 120.25, 126.36,
129.44. MS (m/z): 490.20 (M+ + 1). Anal. Calcd for C33H23N5
(489.25): C, 80.86; H, 4.74; N, 14.32. Found: C, 80.63; H,
4.92; N, 14.04.
Acknowledgments. The authors thank Tamilnadu Pharmaceutical
Sciences Welfare Trust, Chennai, for the financial support. We
also thank our Vice Chancellor Dr. B. Suresh, JSS University,
Mysore, Department of Pharmaceutical Analysis, Department of
Pharmaceutical Biotechnology, JSS College of Pharmacy, Ooty,
and Analytical Instrument Facility (SAIF), IIT Madras, for the
technical support.
N-(4-(5-(3-Nitrophenyl)-1-phenyl-1H-pyrazole-3-yl)phenyl)
acridin-9-amine (6j). Black crystals, yield 59%, mp 259–261ꢀC.
IR (KBr, u, cmÀ1): 3080–3030 (Ar C-H), 1599 and 1506 (Ar
C=C), 1558 and 1373 (NO2), 1273 (C-N), 748 (Ar C-H). 1H
NMR (CDCl3) d ppm: 4.02 (s, 1H, NH), 8.06–6.46 (m, 21H,
Ar-H). 13C NMR: 129.14, 129.81, 126.18, 124.63, 114.78,
148.35, 114.83, 148.27, 149.69, 126.33, 126.41, 129.82,
129.20, 143.08, 116.77, 128.32, 123.07, 128.29, 153.67,
106.13, 144.43, 134.05, 133.61, 122.23, 148.78, 130.17,
121.19, 120.31, 126.40, 129.51. MS (m/z): 534.19 (M+ + 1).
Anal. Calcd for C34H23N5O2 (533.2): C, 76.53; H, 4.36; N,
13.11. Found: C, 76.81; H, 4.15; N, 13.46.
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Bisi, A. J Med Chem 2000, 43, 2007.
[10] Goodell, J. R.; Madhok, A. A.; Hiasa, H.; Ferguson, D. M.
Bioorg Med Chem 2006, 14, 5467.
[11] Bacherikov, V. A.; Chang, J. Y.; Lin, Y. W.; Chen, C. H.; Pan,
W. Y.; Dong, H. Bioorg Med Chem 2005, 13, 6513.
[12] Denny, W. A.; Atwell, G. J.; Baguley, B. C. J Med Chem
1983, 26, 1625.
4-(3-(4-(Acridin-9-ylamino)phenyl)-1-phenyl-1H-pyrazol-5-yl)-
2-methoxyphenol (6k). Brick red crystals, yield 74%, mp
293–295ꢀC. IR (KBr, u, cmÀ1): 3250 (N-H), 3090 (O-H),
3090–3000 (Ar C-H), 1589 and 1506 (Ar C=C), 1273 (C-N),
1
1251 and 1165 (C-O), 748 (Ar C-H). H NMR (CDCl3) d ppm:
4.03 (s, 1H, NH), 5.05 (s, 1H, OH), 3.71 (s, 3H, CH3),
8.02–6.42 (m, 20H, Ar-H). 13C NMR: 129.07, 129.70,
126.31, 124.71, 114.83, 148.32, 114.78, 148.31, 149.80,
126.42, 126.39, 129.76, 129.17, 143.21, 116.82, 128.27,
123.13, 128.33, 153.81, 106.08, 144.37, 139.65, 126.61,
112.65, 151.83, 145.56, 117.39, 121.23, 120.27, 126.42,
129.46, 56.27. MS (m/z): 534.21 (M+). Anal. Calcd for
C35H26N4O2 (534.2): C, 78.62; H, 4.91; N, 10.48. Found: C,
78.52; H, 4.74; N, 10.27.
[13] Su, T. L.; Lin, Y. W.; Chou, T. C.; Zhang, X.; Bacherikov, V.
A.; Chen, C. H. J Med Chem 2006, 49, 3710.
N-(4-(5-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-3-yl)phenyl)
acridin-9-amine (6l). Dark brown crystals, yield 66%, mp
150–152ꢀC. IR (KBr, u, cmÀ1): 3232 (N-H), 3084–3026 (Ar
C-H), 1600 and 1489 (Ar C=C), 1273 (C-N), 1251 and 1165
(C-O), 750 (Ar C-H). 1H NMR (CDCl3) d ppm: 4.07 (s, 1H,
NH), 8.02–6.48 (m, 21H, Ar-H). 13C NMR: 129.12, 129.60,
126.22, 124.63, 114.77, 148.24, 114.83, 148.24, 149.66,
126.42, 126.53, 129.66, 129.76, 143.09, 116.91, 128.31,
123.08, 128.27, 153.70, 106.12, 144.51, 139.77, 128.61,
131.17, 128.83, 129.56, 134.39, 120.18, 139.66, 120.23,
126.22, 129.33. MS (m/z): 523.16 (M+ + 1). Anal. Calcd for
C34H23ClN4 (522.14): C, 78.12; H, 4.46; N, 10.72. Found:
C, 78.27; H, 4.18; N, 10.56.
[14] Harrison, R. J.; Cuesta, J.; Chessari, G.; Read, M. A.; Basra, S.
K.; Reszka, A. P. J Med Chem 2003, 46, 4463.
[15] Gamage, S. A.; Tepsiri, N.; Wilairat, P.; Wojcik, S. J.; Figgitt,
D. P.; Ralph, R. K. J Med Chem 1994, 37, 1486.
[16] Chen, C. H.; Lin, Y. W.; Zhang, X.; Chou, T. C.; Tsai, T. J.;
Kapuriya, N. Eur J Med Chem 2009, 44, 3056.
[17] Atwell, G. J.; Cain, B. F.; Denny, W. A. J Med Chem 1977,
20, 520.
[18] Kapuriya, N.; Kapuriya, K.; Zhang, X.; Chou, T. C.; Kakadiya,
R.; Wu, Y. T. Bioorg Med Chem 2008, 16, 5413.
[19] Hwang, B. Y.; Kim, H. S.; Lee, J. H.; Hong, Y. S.; Lee, K. S.;
Lee, J. J. J Nat Prod 2001, 64, 82.
[20] Philip, S.; Rista, S.; Dominic, S.; Anne, M.; James, M. JNatl
Cancer Inst 1990, 82, 1107.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet