Synthesis and Evaluation of Anticancer Activity
Medicinal Chemistry, 2015, Vol. 11, No. 6 527
rom.), 8.39 (s, 1H, CH=), 9.60 (brs, 1H, OH), 10.66 (s, 1H,
(d, 2H, J = 8.39 Hz, arom.), 7.42 (t, 2H, J = 9.0 Hz, arom.),
1
3
NH). C NMR (100 MHz, DMSO-d
6
): ꢀ 176.4, 169.7,
7.66-7.70 (m, 4H, arom.), 8.13 (s, 1H, CH=), 10.74 (s, 1H
1
3
1
1
55.4, 139.0, 132.9, 132.6, 129.9, 129.0, 127.2, 124.1, 121.6,
6
NH). C NMR (100 MHz, DMSO-d ): ꢀ 177.8, 170.4, 160.7
+
15.3. LCMS (ESI+) m/z 303 (M+H) . Calcd. for
: C, 55.61; H, 3.33; N, 9.26; Found: C, 55.50;
(d, J = 248 Hz), 135.7, 135.1, 132.2 (d J = 9 Hz), 131.0,
130.9, 129.3, 129.3, 127.758, 122.496, 116.6 (d, J = 22 Hz),
C
14
H
10
N
2
O
2
S
2
+
H, 3.10; N, 9.35%.
Z)-5-(3-Phenylallylidene)-4-(4-ethoxyphenylamino)thia-
20.7. LCMS (ESI+) m/z 313 (M+H) . Calcd. for
17 2
C H13FN OS: C, 65.37; H, 4.19; N, 8.97; Found: C, 65.50;
(
ꢀ
1
H, 4.10; N, 8.80%.
zol-2(5H)-one (IIIh). Yield 84%, mp 255-258 C. HNMR
(
(
400 MHz, DMSO-d
6
): ꢀ 1.51 (t, 3H, J = 6.7 Hz, CH
3
), 3.94
(Z)-5-(Furan-2-ylmethylidene)-4-(3-methylphenylamino)
ꢀ
1
m, 2H, OCH ), 7.04 (m, 1H, arom.), 7.30–7.47 (m, 6H,
2
thiazol-2(5H)-one (IIIn). Yield 86%, mp 232-233 C.
H
arom.), 7.49–7.61 (m, 2H, arom.), 7.62–7.76 (m, 4H, arom.),
NMR (400 MHz, DMSO-d ): ꢀ 2.34 (s, 3ꢁ, ꢂꢁ ), 6.79 (d,
6
3
1
3
1
1
1
3
7
0.62 (s, 1H). C NMR (100 MHz, DMSO-d
6
): ꢀ 174.9,
1H, J = 3.7 Hz, furan.), 7.00 (d, 1H, J = 3.6 Hz, furan.), 7.05
(d, 1H, J = 7.6 Hz, arom.), 7.32 (t, 1H, J = 8.0 Hz, arom.),
7.61 (d, 2H, J = 8.4 Hz, arom.), 8.07 (d, 1H, J = 4.0 Hz,
61.5, 159.1, 142.6, 136.8, 136.1, 134.4, 130.3, 129.4, 128.9,
27.9, 127.8, 127.6, 114.8, 63.7, 14.7. LCMS (ESI+) m/z
+
13
51 (M+H) . Calcd. for C20
H
18
N
2
O
2
S: C, 68.55; H, 5.18; N,
furan.), 8.10 (s, 1H, CH=), 10.63 (s, 1H, NH). C NMR (100
.99; Found: C, 68.50; H, 5.10; N, 8.10%.
Z)-5-(4-Chlorophenylmethylidene)-4-(4-fluorophenyl-
MHz, DMSO-d ): ꢀ 178.5, 169.9, 149.7, 147.3, 138.2, 138.1,
6
1
28.8, 126.4, 126.2, 122.6, 119.4, 117.2, 115.9, 113.8, 21.2.
(
+
ꢀ
1
LCMS (ESI+) m/z 285 (M+H) . Calcd. for C H N O S: C,
1
5
12
2
2
amino)thiazol-2(5H)-one (IIIi). Yield 90%, mp >250 C. H
NMR (400 MHz, DMSO-d ): ꢀ 7.31 (t, 2H, J = 8.0 Hz, a-
rom), 7.63 (brs, 4H, arom.), 7.81 (m, 2H, arom.), 8.11 (s, 1H,
6
3.36; H, 4.25; N, 9.85; Found: C, 63.40; H, 4.20; N, 9.95%.
6
(Z)-5-(4-Chlorophenylmethylidene)-4-(2-hydroxyphenyl-
13
ꢀ
CH=), 10.86 (s, 1H, NH). C NMR (100 MHz, DMSO-d
6
):
amino)thiazol-2(5H)-one (IIIo). Yield 76%, mp 234-236 C.
1
ꢀ
1
2
177.7, 170.7, 159.6 (d, J = 243 Hz), 134.8, 134.6, 133.1,
H NMR (400 MHz, DMSO-d ): ꢀ 6.87 (m, 1H, arom.), 6.97
6
31.4, 130.1, 129.6, 127.8, 124.7 (d, J = 9 Hz), 115.7 (d, J =
(m, 1H, arom.), 7.17 (m, 1H, thiophen.), 7.40 (m, 1H,
arom.), 7.62 (brs, 4H, arom.), 8.11 (s, 1H, CH=), 9.95 (brs,
+
3 Hz). LCMS (ESI+) m/z 333/335 (M+H) . Calcd. for
1
3
C
16
H
10ClFN
2
OS: C, 57.75; H, 3.03; N, 8.42; Found: C,
1
d
1
H, OH), 10.54 (brs, 1H, NH). C NMR (100 MHz, DMSO-
5
7.80; H, 2.90; N, 8.50%.
Z)-5-(Thiophen-2-ylmethylidene)-4-(4-fluorophenyl-
6
): ꢀ 177.0, 172.6, 151.5, 134.6, 133.2, 131.4, 129.9, 129.5,
28.4, 127.4, 127.2, 125.2, 119.1 116.4. LCMS (ESI+) m/z
(
+
ꢀ
331/333 (M+H) . Calcd. for C H ClN O S: C, 58.10; H,
1
6
11
2
2
amino)thiazol-2(5H)-one (IIIj). Yield 78%, mp 277-278 C.
1
3
.35; N, 8.47; Found: C, 58.20; H, 3.30; N, 8.40%.
Z)-5-(4-Diethylaminophenylmethylidene)-4-(4-hydroxy-
-isopropyl-2-methylphenylamino)thiazol-2(5H)-one (IIIp).
H NMR (400 MHz, DMSO-d
arom.), 7.29 (t, 1H, J = 3.6 Hz, thiophen.), 7.50 (d, 1H, J =
.6 Hz, thiophen.), 7.81-7.84 (m, 2H, arom.), 7.94 (d, 1H, J
4.8 Hz, thiophen.), 8.40 (s, 1H, CH=), 10.73 (s, 1H, NH).
6
): ꢀ 7.22 (t, 2H, J = 8.8 Hz,
(
3
5
ꢀ
1
=
Yield 54%, mp 255-258 C. H NMR (400 MHz, DMSO-d
6
):
), 3.18 (m, 1H,
), 6.70 (s, 1H, a-
rom.), 6.83 (d, 2H, J = 8.4 Hz, arom), 6.98 (s, 1H, arom.),
1
3
C NMR (100 MHz, DMSO-d
243 Hz), 138.8, 134.7, 133.2 (d, J = 44 Hz), 129.1, 126.8,
6
): ꢀ 176.8, 170.2, 159.5 (d, J
ꢀ
1.15 (m, 12H, 4*CH
3 3
), 2.07 (s, 3H, CH
=
CHMe ), 3.43 (q, 4H, J = 6.7 Hz, 2*CH
2
2
1
3
9
24.5, 124.4, 122.5, 115.6 (d, J = 23 Hz). LCMS (ESI+) m/z
+
05 (M+H) . Calcd. for C14
9 2 2
H FN OS : C, 55.25; H, 2.98; N,
7
1
d
1
1
.41 (d, 2H, J = 8.3 Hz, arom.), 7.91 (s, 1H, CH=), 9.39 (s,
13
.20; Found: C, 55.35; H, 3.00; N, 9.10%.
H, OH), 10.30 (s, 1H, NH). C NMR (100 MHz, DMSO-
6
): ꢀ 177.9, 173.0, 153.5, 148.8, 132.3, 132.2, 129.3, 128.4,
(
Z)-5-(Furan-2-ylmethylidene)-4-(4-chlorophenylamino)
ꢀ 1
24.4, 120.5, 120.3, 116.5, 111.7, 43.9, 26.3, 22.6, 17.6,
thiazol-2(5H)-one (IIIk). Yield 68%, mp >250 C. H NMR
400 MHz, DMSO-d ): ꢀ 6.74 (brs, 1H, furan.), 6.95 (d, 1H,
J = 4.2 Hz, furan.), 7.44 (d, 2H, J = 8.8 Hz, arom.), 7.86 (d,
H, J = 8.8 Hz, arom.), 7.99 (brs, 1H, furan.), 8.06 (s, 1H,
+
2.6. LCMS (ESI+) m/z 424 (M+H) . Calcd. for
(
6
24 29 3 2
C H N O S: C, 68.05; H, 6.90; N, 9.92; Found: C, 68.00;
H, 6.80; N 10.00%.
Z)-5-(4-Dimethylaminophenylmethylidene)-4-(4-hydro-
xy-5-isopropyl-2-methylphenylamino)thiazol-2(5H)-one (II-
2
13
CH=), 10.67 (s, 1H, NH). C NMR (100 MHz, DMSO-d
6
):
178.6, 169.8, 149.6, 147.5, 137.3, 129.3, 128.8, 126.1,
23.7, 117.5, 116.2, 113.8. LCMS (ESI+) m/z 305/307
(
ꢀ
1
ꢀ
1
Iq). Yield 68%, mp >250 C. H NMR (400 MHz, DMSO-
): ꢀ 1.20 (d, 6H, 2*CH ), 2.15 (s, 3H, CH ), 3.23 (m, 1H,
+
(
M+H) . Calcd. for C14
.19; Found: C, 55.20; H, 3.10; N, 9.00%.
H
9
ClN
2 2
O S: C, 55.18; H, 2.98; N,
d
6
3
3
9
2
CHMe ), 6.75 (s, 1H, arom.), 6.98 (s, 1H, arom.), 7.49 (d,
(
Z)-5-(Thiophen-2-ylmethylidene)-4-(4-chlorophenylami-
2H, J = 8.4 Hz, arom), 7.53 (d, 2H, J = 8.4 Hz, arom.) 7.90
ꢀ
1
13
no)thiazol-2(5H)-one (IIIl). Yield 63%, mp >250 C.
H
(s, 1H, CH=), 9.10 (s, 1H, OH), 10.30 (s, 1H, NH). C NMR
NMR (400 MHz, DMSO-d
6
): ꢀ 7.28 (t, 1H, J = 4.0 Hz, thio-
6
(100 MHz, DMSO-d ): ꢀ 177.4, 172.8, 152.8, 147.6, 134.8,
pen.), 7.45 (d, 2H, J = 8.0 Hz, arom.), 7.51 (d, 1H, J = 4.0
133.1, 131,9, 129.2, 128.6, 123.7, 120.6, 120.2, 116.0, 111.7,
+
Hz, thiophen.), 7.86 (d, 2H, J = 8.0 Hz, arom.), 8.42 (s, 1H,
41.2, 26.8, 23.4, 17.8. LCMS (ESI+) m/z 396 (M+H) .
13
CH=), 10.73 (s, 1H, NH). C NMR (100 MHz, DMSO-d
6
):
25 3 2
Calcd. for C22H N O S: C, 66.81; H, 6.37; N, 10.62; Found:
ꢀ
176.9, 170.0, 138.8, 137.3, 133.6, 133.2, 129.4, 129.1,
C, 66.50; H, 6.50; N 10.60%.
1
28.9, 126.8, 123.8, 122.8. LCMS (ESI+) m/z 321/323
+
Crystal Structure Determination of (Z)-5-(4-diethylamino-
phenylmethylidene)-4-(4-hydroxy-5-isopropyl-2-methylphe-
nylamino)thiazol-2(5H)-one Ethanol Solvate (IIIq)
(
M+H) . Calcd. for C14
H
9
ClN
2 2
OS : C, 52.41; H, 2.83; N,
8
.73; Found: C, 52.50; H, 3.00; N, 8.60%.
(
Z)-5-(4-Fluorophenylmethylidene)-4-(4-methylphenyl-
ꢀ
Crystal data: C22
H
25
N
3
O
2
S, 1/3(C
2
H
6
r
O), M = 410.87,
amino)thiazol-2(5H)-one (IIIm). Yield 74%, mp 272-274 C.
1
monoclinic, space group C2/c, a= 20.592(3), b= 13.8421(8),
6 3
H NMR (400 MHz, DMSO-d ): ꢀ 2.33 (s, 3H, CH ), 7.26