4
Y. SHEPETA ET AL.
(
1
100 MHz, DMSO-d ): 37.5 (CH ), 113.5, 116.5, 121.2, 125.2, 122.1, 123.8, 124.3, 125.7, 128.4, 129.8 (d, J ¼ 30.0 Hz, C–F),
6
2
25.7, 127.9, 129.6, 130.1, 130.8, 137.6, 143.3 (¼CH), 154.6 130.9, 131.3, 133.1, 137.6, 141.2, 143.3 (¼CH), 152.4
(
C ¼ O), 164.2 (C ¼ O), 170.2 (C ¼ O). Anal. Calcd for (C ¼ O), 162.8 (d, J ¼ 300.0 Hz, C–F), 169.4 (C ¼ O), 170.5
C H Cl N O S: C, 49.41; H, 3.23; N, 12.81. Found: C, (C ¼ S). Anal. Calcd for C H Cl FN O S : C, 52.66; H,
1
8
14
2
4
3
24 17
2
4 2 2
þ
4
9.48; H, 3.29; N, 12.72. ESI-MS m/z 436/438 (M þ H) .
3.13; N, 10.23. Found: C, 52.72; H, 3.19; N, 10.32. ESI-MS
þ
[
2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid N ꢀ- (4- m/z 546/548 (M þ H) .
oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-hydrazide
Yield 80%, gray powder, mp 193–194 C (AcOH). H NMR oxo-2-thioxo-3-(3-trifluoromethylphenyl)thiazolidin-5-ylidene-
(3.3).
[2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid N ꢀ- (4-
ꢂ
1
(
400 MHz, DMSO-d ): d 3.70 (s, 2H, CH ), 6.32 (d, 1H, methyl)-hydrazide (3.7). Yield 77%, yellow powder, mp
6 2
ꢂ
1
J ¼ 7.9 Hz, arom.), 6.89 (t, 1H, J ¼ 7.4 Hz, arom.), 7.05–7.10 208–209 C (AcOH). H NMR (400 MHz, DMSO-d
m, 2H, arom.), 7.17 (t, 1H, J ¼ 7.9 Hz, arom.), 7.25 (t, 1H, 2H, CH ), 6.33 (d, 1H, J ¼ 7.4 Hz, arom.), 6.90 (t, 1H,
J ¼ 7.4 Hz, arom.), 7.50–7.53 (m, 3H, CH, NH, arom.), 9.87 J ¼ 7.4 Hz, arom.), 7.08 (t, 1H, J ¼ 6.8 Hz, arom.), 7.17 (t, 1H,
): d 3.76 (s,
6
(
2
1
3
(
s, 1H, NH), 10.92 (s, 1H, NH), 12.93 (s, 1H, NH).
C
J ¼ 7.8 Hz, arom.), 7.29 (d, 1H, J ¼ 6.8 Hz, arom.), 7.51 (s, 1H,
NMR (100 MHz, DMSO-d ): 37.5 (CH ), 116.7, 121.3, 124.4, CH), 7.52 (s, 1H, NH), 7.62 (d, 1H, J ¼ 7.4 Hz, arom.),
6
2
1
1
25.8, 128.2, 129.6, 130.0, 131.2, 137.5, 143.3, 145.4 (¼CH), 7.75–7.76 (m, 4H, arom.), 7.83 (d, 2H, J ¼ 7.8Hz, arom.), 10.09
13
52.4 (C ¼ O), 166.4 (C ¼ O), 171.9 (C ¼ O). Anal. Calcd for (s, 1H, NH), 11.03 (s, 1H, NH). C NMR (100 MHz, DMSO-
): 36.2 (CH ), 117.1, 121.7, 129.7, 131.2, 133.2, 134.1, 136.7,
137.5, 139.0, 139.4, 140.4, 140.9, 141.7, 143.1, 147.0 (¼CH),
C H Cl N O S : C, 47.69; H, 3.11; N, 12.36. Found: C,
d
6
2
1
8
14
2 4 4 2
þ
4
7.58; H, 3.20; N, 12.42. ESI-MS m/z 452/454 (M þ H) .
[
2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid N ꢀ- (3- 152.3 (C ¼ O), 166.5 (C ¼ O), 178.7 (C ¼ S). Anal. Calcd for
ethyl-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-hydrazide
C
25
H
17Cl
2
F
3
N
4
O
2
S
2
: C, 50.26; H, 2.87; N, 9.38. Found: C, 50.32;
ꢂ
1
þ
(
3.4). Yield 70%, gray powder, mp 212–213 C (AcCN). H H, 2.79; N, 9.32. ESI-MS m/z 596/598 (M þ H) .
NMR (400 MHz, DMSO-d ): d 1.09 (t, 3H, J ¼ 6.4 Hz, CH ),
N-f4-[5-(N ꢀ- f2-[2-(2,6-Dichloro-phenylamino)-phenyl]-
6
3
3
(
7
.72 (s, 2H, CH ), 3.94 (q, 2H, J ¼ 6.4, 13.4 Hz, CH ), 6.31 acetylg-hydrazinomethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-
2
2
d, 1H, J ¼ 8.0 Hz, arom.), 6.89 (d, 1H, J ¼ 7.3 Hz, arom.), phenylg-acetamide (3.8). Yield 80%, orange powder, mp
ꢂ
1
.07 (t, 1H, J ¼ 7.3 Hz, arom.), 7.15 (t, 1H, J ¼ 8.0 Hz, 190–191 C (DMF:EtOH). H NMR (400 MHz, DMSO-d
), 3.75 (s, 2H, CH
), 6.33 (d, 1H, J ¼ 8.0 Hz,
arom.), 7.71 (m, NH, CH), 10.02 (s, 1H, NH), 10.99 (s, 1H, arom.), 6.90 (t, 1H, J ¼ 7.6 Hz, arom.), 7.09 (t, 1H,
): d
6
arom.), 7.25 (d, 1H, J ¼ 7.3 Hz, arom.), 7.49–7.51 (m, 2H, 2.07 (s, 3H, CH
3
2
1
3
NH). C NMR (100 MHz, DMSO-d ): 12.4 (CH ), 37.5 J ¼ 8.0 Hz, arom.), 7.17–7.19 (m, 3H, arom.), 7.28 (d, 1H,
6
3
(
1
(
4
CH ), 39.1 (CH ), 116.8, 121.3, 124.3, 125.8, 128.2, 129.6, J ¼ 7.6 Hz, arom.), 7.51 (s, 1H, CH), 7.53 (s, 1H, NH), 7.66
3
2
30.0, 131.2, 137.5, 143.3 (¼CH), 156.0 (C ¼ O), 164.7 (d, 2H, J ¼ 8.8 Hz, arom.), 7.76–7.80 (m, 2H, arom.), 10.07
13
C ¼ O), 171.9 (C ¼ S). Anal. Calcd for C H Cl N O S : C, (s, 1H, NH), 11.06 (s, 1H, NH). C NMR (100 MHz,
19
16
2 4 2 2
8.83; H, 3.45; N, 11.99. Found: C, 48.73; H, 3.40; N, 11.92. DMSO-d
): 21.4 (CH
6
), 37.4 (CH
3
), 117.8, 121.8, 123.6,
2
þ
ESI-MS m/z 480/482 (M þ H) .
124.8, 125.9, 128.5, 129.9, 130.1, 130.5, 131.6, 133.8, 137.6,
[
2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid N ꢀ- (4- 141.4, 143.5 (¼CH), 151.5 (C ¼ O), 160.9 (C ¼ O), 164.7
oxo-2-thioxo-3-p-tolyl-thiazolidin-5-ylidenemethyl)-hydrazide
(C ¼ O), 171.6 (C ¼ S). Anal. Calcd for C26 : C,
H
21Cl N O S
2 5 3 2
ꢂ
(
3.5). Yield 83%, orange powder, mp 156–157 C (AcOH). 53.24; H, 3.61; N, 11.94. Found: C, 53.32; H, 3.74; N, 11.82.
1
þ
H NMR (400 MHz, DMSO-d ): d 2.30 (s, 3H, CH ), 3.75 ESI-MS m/z 585/587 (M þ H) .
6
3
(
s, 2H, CH ), 6.33 (d, 1H, J ¼ 7.6 Hz, arom.), 6.90 (t, 1H,
Acetic acid 3-[5-(N ꢀ- f2-[2-(2,6-dichloro-phenylamino)-phe-
2
J ¼ 7.6 Hz, arom.), 7.06–7.11 (m, 3H, arom.), 7.16 (d, 1H, nyl]-acethylg-hydrazinomethylene)-4-oxo-2-thioxo-thiazolidin-
J ¼ 8.0 Hz, arom.), 7.19–7.30 (m, 3H, arom.), 7.52 (d, 2H, 3-yl]-phenyl ester (3.9). Yield 88%, orange powder, mp
ꢂ
1
J ¼ 8.0 Hz, arom.), 7.75 (s, 1H, NH), 7.84 (s, 1H, CH), 10.08 151–152 C (AcOH). H NMR (400 MHz, DMSO-d
): d 2.29
6
13
(
s, 1H, NH), 11.05 (s, 1H, NH). C NMR (100 MHz, (s, 3H, CH ), 3.76 (s, 2H, CH
3 2
), 6.39 (d, 1H, J ¼ 7.6 Hz,
DMSO-d ): 21.4 (CH ), 37.3 (CH ), 116.7, 121.1, 123.0, arom.), 6.91 (t, 1H, J ¼ 7.1 Hz, arom.), 7.09 (t, 1H,
6
3
2
1
1
24.0, 125.2, 128.5, 129.6, 130.0, 130.1, 131.1, 133.2, 137.1, J ¼ 7.1 Hz, arom.), 7.17 (t, 1H, J ¼ 8.0 Hz, arom.), 7.25–7.30
41.4, 142.3 (¼CH), 152.1 (C ¼ O), 169.3 (C ¼ O), 172.0 (m, 5H, arom.), 7.52 (d, 2H, J ¼ 8.0 Hz, arom.), 7.76–7.78
(
C ¼ S). Anal. Calcd for C H Cl N O S : C, 55.25; H, 3.71; (m, 2H, CH. NH), 10.07 (s, 1H, NH), 11.05 (s, 1H, NH).
25
20
2 4 4 2
13
N, 10.31. Found: C, 55.18; H, 3.39; N, 10.42. ESI-MS m/z
C NMR(100 MHz, DMSO-d ): 21.4 (CH ), 37.0 (CH ),
6 3 2
þ
5
42/544 (M þ H) .
116.0, 121.1, 123.4, 124.4, 125.1, 128.3, 129.6, 130.3, 130.6,
[
2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid Nꢀ-[3-(4- 131.4, 133.9, 137.6, 143.3 (¼CH), 151.4 (C ¼ O), 169.1
fluorophenyl)-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-
(C ¼ O), 169.5 (C ¼ O), 172.0 (C ¼ S). Anal. Calcd for
ꢂ
hydrazide (3.6). Yield 83%, yellow powder, mp 177–178 C
C
26
H20Cl
2
N O
4
4
S
2
: C, 53.16; H, 3.43; N, 9.54. Found: C,
1
þ
(
AcOH). H NMR (400 MHz, DMSO-d ): d 3.76 (s, 2H, 53.22; H, 3.50; N, 9.60. ESI-MS m/z 586/588 (M þ H) .
6
CH ), 6.33 (d, 1H, J ¼ 8.4 Hz, arom.), 6.90 (t, 1H, J ¼ 7.2 Hz,
2
arom.), 7.09 (t, 1H, J ¼ 7.2 Hz, arom.), 7.17 (t, 1H,
J ¼ 8.0 Hz, arom.), 7.29 (d, 1H, J ¼ 8.4 Hz, arom.), 7.32–7.34
Pharmacology
(
m, 4H, arom.), 7.52 (d, 2H, J ¼ 8.0 Hz, arom.), 7.81 (s, 1H, In vitro anticancer assay
NH), 7.82 (s, 1H, CH), 10.10 (s, 1H, NH), 11.08 (s, 1H, Anticancer in vitro assay was performed on a panel of
1
3
NH). C NMR (100 MHz, DMSO-d ): 37.7 (CH ), 116.5, approximately 60 human tumor cell lines derived from nine
6
2