4
Journal of Chemistry
1
775 cm−1; H NMR (d -DMSO, 500 MHz): ꢃ 12.28 (s, 1H,
1H NMR (d -DMSO, 500 MHz): ꢃ 12.22 (s, 1H, NH), 7.88
6
6
NH), 8.13 (s, 1H, CH), 8.10 (d, 1H, J = 7.7 Hz, Ar), 7.53 (d, 1H,
J = 7.8 Hz, Ar), 7.17–7.50 (m, 11H, Ar), 4.41 (s, 1H, CH), 3.66
(s, 2H, NCH ), 3.36 (t, 2H, J = 4.5 Hz, NCH ), 2.43 (t, 2H,
(s, 1H, Ar), 7.15–7.44 (m, 13H, Ar), 4.38 (s, 1H, CH), 3.66
(s, 2H, NCH ), 3.33 (s, 2H, NCH ), 2.59 (s, 3H, CH ), 2.41
2
2
3
(s, 2H, NCH ), 2.22 (s, 2H, NCH ); ESI-MS, m/z(%): 438.2
2
2
2
2
J = 4.7 Hz, NCH ), 2.26 (s, 2H, NCH ); ESI-MS, m/z(%):
[(M+H)+, 100]; Anal. calcd for C H N O : C, 76.86; H,
2
2
28 27
3
2
504.4 [(M+2)+, 100], 502.4 [(M+H)+, 100]; Anal. calcd for
C H BrN O : C, 64.55; H, 4.81; N, 8.36; O, 6.37; Found: C,
6.22; N, 9.60; O, 7.31; Found: C, 76.89; H, 6.21; N, 9.62; O, 7.30.
27 24
3
2
1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazine-1-yl)-2-(2-
64.53; H, 4.82; N, 8.35; O, 6.38.
methyl-1H-indol-3-yl)ethane-1,2-dione (28). A gray solid
1-(4-Benzhydrylpiperazine-1-yl)-2-(5-bromo-1H-indol-3-yl)eth-
(85%, mp 180∼182∘C); IR 3180, 3103, 3058, 2974, 1610, 1492,
ane-1,2-dione (23). A pale white solid (53%, mp 238∼240∘C);
1457, 1247, 986, 790 cm−1; H NMR (d -DMSO, 500 MHz):
1
6
IR 3154, 3083, 3061, 2970, 1617, 1477, 1438, 1232, 998, 807 cm−1;
ꢃ 12.22 (s, 1H, NH), 7.87 (s, 1H, Ar), 7.14–7.44 (m, 12H, Ar),
1H NMR (d -DMSO, 500 MHz): ꢃ 12.46 (s, 1H, NH), 8.19–
4.43 (s, 1H, CH), 3.66 (s, 2H, NCH ), 3.33 (s, 2H, NCH ),
6
2
2
2
8.21 (m, 2H, Ar+CH), 7.50 (d, 1H, J = 8.6 Hz, Ar), 7.18–7.43
2.59 (s, 3H, NCH ), 2.42 (s, 2H, NCH ), 2.24 (s, 2H, NCH );
2
2
2
(m, 11H, Ar), 4.38 (s, 1H, CH), 3.65 (s, 2H, NCH ), 3.37 (t,
ESI-MS, m/z(%): 474.3 [(M+2)+, 40], 472.5 [(M+H)+, 100];
2
2H, J = 4.7 Hz, NCH ), 2.43 (t, 2H, J = 4.7 Hz, NCH ), 2.27
Anal. calcd for C H ClN O : C, 71.25; H, 5.55; N, 8.90; O,
2
2
28 26
3
2
(s, 2H, NCH ); ESI-MS, m/z(%): 504.4 [(M+2)+, 100], 502.4
6.78; Found: C, 71.26; H, 5.54; N, 8.89; O, 6.79.
[(M+H)+, 100]; Anal. calcd for C H BrN O : C, 64.55; H,
27 24
3
2
1-(4-((4-Fluorophenyl)(phenyl)methyl)piperazine-1-yl)-2-(2-
methyl-1H-indol-3-yl)ethane-1,2-dione (29). A gray solid
(79%, mp >300∘C); IR 3185, 3085, 3057, 2973, 1616, 1508, 1437,
4.81; N, 8.36; O, 6.37; Found: C, 64.57; H, 4.80; N, 8.34; O,
6.38.
1245, 986, 800 cm−1; 1H NMR (d -DMSO, 500 MHz): ꢃ 12.22
1-(5-Bromo-1H-indol-3-yl)-2-(4-((4-chlorophenyl)(phe-
6
nyl)methyl)piperazine-1-yl)ethane-1,2-dione (24). A white
(s, 1H, NH), 7.88 (s, 1H, Ar), 7.11–7.46 (m, 12H, Ar), 4.39 (s,
1H, CH), 3.66 (s, 2H, NCH ), 3.33 (s, 2H, NCH ), 2.59 (s,
solid (81%, mp 240∼242∘C); IR 3164, 3061, 3028, 2922,
2
2
1620, 1489, 1447, 1234, 954, 804 cm−1; H NMR (d -DMSO,
1
6
3H, CH ), 2.41 (s, 2H, NCH ), 2.22 (s, 2H, NCH ); ESI-MS,
3
2
2
m/z(%): 456.5 [(M+2)+, 60], 457.4 [(M+2)+, 100]; Anal. calcd
500 MHz): ꢃ 12.46 (s, 1H, NH), 8.19–8.21 (m, 2H, Ar+CH),
7. 5 0 (d, 1H, J = 8.6 Hz, Ar), 7.19–7.46 (m, 11H, Ar), 4.43 (s,
1H, CH), 3.65 (s, 2H, NCH ), 3.37 (s, 2H, NCH ), 2.42 (s,
for C H FN O : C, 73.83; H, 5.75; N, 9.22; O, 7.02; Found:
28 26
3
2
2
2
C, 73.81; H, 5.75; N, 9.21; O, 7.03.
2H, NCH ), 2.26 (s, 2H, NCH ); ESI-MS, m/z(%): 540.3
2
2
[(M+4)+, 30], 538.3 [(M+2)+, 100], 536.3 [(M+H)+, 70]; Anal.
1-(4-((4-Bromophenyl)(phenyl)methyl)piperazine-1-yl)-2-(2-
calcd for C H BrClN O : C, 60.41; H, 4.32; N, 7.83; O, 5.96;
27 23
3
2
methyl-1H-indol-3-yl)ethane-1,2-dione (30). A gray solid
(79%, mp 181∼183∘C); IR 3182, 3085, 3057, 2970, 1612, 1491,
Found: C, 60.44; H, 4.31; N, 7.84; O, 5.95.
1
1453, 1246, 986, 789 cm−1; H NMR (d -DMSO, 500 MHz):
6
1-(5-Bromo-1H-indol-3-yl)-2-(4-((4-fluorophenyl)(phenyl)meth-
yl)piperazine-1-yl)ethane-1,2-dione (25). A white solid (82%,
mp 251∼253∘C); IR 3156, 3064, 3031, 2964, 1624, 1478, 1437,
ꢃ 12.22 (s, 1H, NH), 7.87 (s, 1H, Ar), 7.15–7.49 (m, 12H, Ar),
4.39 (s, 1H, CH), 3.66 (s, 2H, NCH ), 3.38 (s, 2H, NCH ),
2
2
1232, 999, 806 cm−1; 1H NMR (d -DMSO, 500 MHz): ꢃ 12.46
2.58 (s, 3H, CH ), 2.42 (s, 2H, NCH ), 2.24 (s, 2H, NCH );
3
2
2
6
ESI-MS, m/z(%): 518.4 [(M+2)+, 50], 516.4 [(M+H)+, 100];
(s, 1H), 8.20–8.21 (m, 2H, Ar+CH), 7.50 (d, 1H, J = 8.6 Hz,
Ar), 7.11–7.47 (m, 11H, Ar), 4.42 (s, 1H, CH), 3.65 (s, 2H,
NCH ), 3.36 (s, 2H, NCH ), 2.42 (s, 2H, NCH ), 2.26 (s,
Anal. calcd for C H BrN O : C, 65.12; H, 5.07; N, 8.14; O,
28 26
3
2
6.20; Found: C, 65.15; H, 5.06; N, 8.15; O, 6.19.
2
2
2
2H, NCH ); ESI-MS, m/z(%): 522.4 [(M+2)+, 100], 520.4
2
[(M+H)+, 100]; Anal. calcd for C H BrFN O : C, 62.32; H,
3.3. Treatment of Tumor Cell Lines. e antiproliferative
activity of compounds 19–30 against several human cancer
cell lines was assayed by standard MTT assay procedures.
27 23
3
2
4.45; N, 8.07; O, 6.15; Found: C, 62.33; H, 4.45; N, 8.08; O,
6.14.
Cells were cultured in DMEM medium at 37∘C with 5% CO
2
1-(5-Bromo-1H-indol-3-yl)-2-(4-((4-bromophenyl)(phe-
and 95% air, supplemented with 10% (V/V) bovine calf serum
[14]. Cells were plated in 96-well plates at the density of 10,000
cells per well. Afer 24 h, the cells were treated with various
concentrations of compounds from 1.0 to 100.0 ꢁg/mL. Wells
containing culture medium without cells were used as blanks
and cisplatin was assayed at the same time as a positive con-
trol. e cells were further incubated for 72 h. e cytotoxicity
was measured by adding 5 mg/mL of MTT to each well and
incubated for another 4 h. e formazan crystals were dis-
solved by adding 150 ꢁL of DMSO to each well. e optical
density of each well was then measured on a microplate
nyl)methyl)piperazine-1-yl)ethane-1,2-dione (26). A white
solid (78%, mp 227∼229∘C); IR 3158, 3082, 3060, 2970,
1617, 1477, 1437, 1233, 998, 807 cm−1; H NMR (d -DMSO,
1
6
500 MHz): ꢃ 12.46 (s, 1H, NH), 8.20–8.21 (m, 2H, Ar), 7.51 (d,
1H, J = 8.6 Hz, Ar), 7.18–7.49 (m, 11H, Ar), 4.41 (s, 1H, CH),
3.65 (s, 2H, NCH ), 3.37 (t, 2H, J = 4.5 Hz, NCH ), 2.42 (t,
2
2
2H, J = 4.6 Hz, NCH ), 2.27 (s, 2H, NCH ); ESI-MS, m/z(%):
2
2
584.2 [(M+4)+, 50], 582.3 [(M+2)+, 100], 580.3 [(M+H)+,
50]. Anal. calcd for C H Br N O : C, 55.79; H, 3.99; N,
27 23
2
3
2
7.23; O, 5.50; Found: C, 55.81; H, 4.00; N, 7.22; O, 5.51.
1-(4-Benzhydrylpiperazine-1-yl)-2-(2-methyl-1H-indol-3-
yl)ethane-1,2-dione (27). A gray solid (78%, mp 199∼201∘C);
IR 3180, 3103, 3058, 2974, 1610, 1492, 1457, 1246, 986, 790 cm−1;
spectrophotometer at a wavelength of 570 nm. e IC value
50
(ꢁg/mL) was determined from plots of % viability against
dose of compound added.