Article
Journal of Medicinal Chemistry, 2010, Vol. 53, No. 8 3045
as eluent (1/1 to 0/1). This afforded the expected derivative 1a as
a white solid at 92% yield: mp = 161 ꢀC. 1H NMR (DMSO-d6):
δ = 10.37 (s, 1H), 9.86 (s, 1H), 8.70 (s, 1H), 7.66-6.99 (m, 5H),
2.52-2.50 (m, 1H), 2.31-2.22 (m, 2H), 1.99-1.88 (m, 2H),
1.58-1.06 (m, 8H). 13C NMR (DMSO-d6): δ = 171.67, 169.58,
139.54, 129.00, 123.32, 119.42, 36.71, 32.59, 28.74, 25.38.
C14H20N2O3. MS (ESIþ) m/z 264.1474 (100%, (M þ Hþ)).
Compound 1b. Yellow oil crystallizing on standing: mp = 142 ꢀC.
1H NMR (DMSO-d6): δ = 9.43 (s, 1H), 7.21-7.18 (m, 2H),
6.50-6.47 (m, 2H), 2.51 (s, 1H), 2.22-1.92 (m, 4H), 1.48-1.26
(m, 10H). 13C NMR (DMSO-d6): δ = 171.18, 170.08, 145.42,
129.50, 121.80, 114.70, 37.07, 33.14, 30.27, 29.34, 29.30, 26.15,
25.95. C14H 21N3O3. MS (ESIþ) m/z 279.1583(100%, (M þ Hþ)).
Compound 1c. Yellow oil crystallizing on standing: mp =
29.30, 25.97. C15H19N3O3. MS (ESIþ) m/z 289.1426 (100%,
(M þ Hþ)).
Compound 1m. Yellow oil crystallizing on standing: mp =
172 ꢀC. 1H NMR (DMSO-d6): δ = 9.19 (s, 1H), 7.43-7.31
(m, 9H), 2.29-1.18 (m, 14H). 13C NMR (DMSO-d6): δ =
174.98, 171.91, 145.28, 140.04, 139.40, 135.26, 130.36, 129.10,
128.61, 127.11, 126.12, 117.12, 115.60, 32.60, 28.69, 25.40.
C20H24N2O3. MS (ESIþ) m/z 340.1787 (100%, (M þ Hþ)).
Compound 1n. Brown solid: mp = 128 ꢀC. 1H NMR (DMSO-
d6): δ = 9.52 (s, 1H), 7.37-7.34 (d, J = 12 Hz, 2H), 6.66-6.63
(d, J = 8 Hz, 2H), 2.80 (s, 6H), 2.52-1.23 (m, 14H). 13C NMR
(DMSO-d6): δ = 171.12, 169.80, 147.37, 125.37, 121.10, 112.99,
36.52, 32.57, 28.65, 25.50, 25.34. C16H25N3O3. MS (ESIþ) m/z
307.1896 (100%, (M þ Hþ)).
1
122 ꢀC. H NMR (DMSO-d6): δ=9.43 (s, 1H), 7.21-7.18 (m,
Compound 1o. White solid: mp = 110 ꢀC. 1H NMR (DMSO-
d6): δ = 7.96-7.93 (d, J = 12 Hz, 2H), 6.71-6.59 (m, 2H),
2.51-1.10 (m, 12H). 13C NMR (DMSO-d6): δ = 176.58, 169.58,
156.05, 136.98, 126.74, 112.74, 34.91, 32.57, 28.70, 25.37, 25.17.
C14H19N3O5. MS (ESIþ) m/z 309.3215 (100%, (M þ Hþ)).
Compound 1p. White solid: mp = 124 ꢀC. 1H NMR (DMSO-
d6): δ = 10.12 (s, 1H), 8.31 (s, 1H), 7.85-7.35 (m, 7H), 2.52-1.22
(m, 13H). 13C NMR (DMSO-d6): δ = 172.00, 169.61, 137,25,
133.81, 129.98, 128.61, 127.77, 127.57, 126.71, 124.79, 120.35,
115.38, 36.79, 32.61, 28.76, 25.40. C18H22N2O3. MS (ESIþ) m/z
314.1630 (100%, (M þ Hþ)).
2H), 6.50-6.47 (m, 2H), 2.51 (s, 1H), 2.22-1.92 (m, 4H), 1.48-
1.26 (m, 10H). 13C NMR (DMSO-d6): δ = 175.03, 172.87, 155.43,
131.03, 119.06, 116.37, 37.48, 32.12, 24.82, 24.75, 23.61. C14H20-
N2O 4. MS (ESIþ) m/z 280.1423 (100%, (M þ Hþ)).
Compound 1d. Yellow oil crystallizing on standing: mp =
154 ꢀC. 1H NMR (DMSO-d6): δ = 10.37 (s, 1H), 10.08 (s, 1H),
7.63-6.90 (m, 4H), 2.52-2.23 (m, 3H), 2.02-1.86 (m, 2H),
1.59-1.26 (m, 8H). 13C NMR (DMSO-d6): δ = 172.04, 169.58,
162.45, 141.40, 130.51, 115.04, 1109.63, 106.12, 36.73, 32.58,
28.71, 25.37, 25.24. C14H19FN O3. MS (ESIþ) m/z 282.1383
2
Compound 1q. Pale viscous yellow oil. 1H NMR (DMSO-d6):
δ = 7.74-7.27 (m, 7H), 2.28-1.31 (m, 14H). 13C NMR (DMSO-
d6): δ = 179.80, 172.54, 143.65, 137.14, 128.18, 127.30, 124.82,
118.07, 111.67, 35.97, 32.95, 29.29, 29.09. C17H21N3O3. MS
(ESIþ) m/z 315.1583 (100%, (M þ Hþ)).
(100%, (M þ Hþ)).
Compound 1e. Pale viscous yellow oil: 1H NMR (DMSO-d6):
δ = 9.95 (s, 1H), 7.61-7.08 (m, 4H), 2.51-1.26 (m, 14H). 13
C
NMR (DMSO-d6): δ = 173.86, 171.67, 135.96, 121.28, 121.15,
115.66, 115.36, 36.53, 33.55, 28.69, 28.51, 25.34, 24.62.
C14H19FN2O3. MS (ESIþ) m/z 282.1383 (100%, (M þ Hþ)).
Compound 1f. Yellow oil crystallizing on standing: mp = 52
ꢀC. 1H NMR (DMSO-d6): δ = 9.60 (s, 1H), 7.38-7.34 (m, 2H),
6.99-6.44 (m, 4H), 2.52-2.50 (m, 1H), 2.25-1.93 (m, 4H),
1.58-1.22 (m, 7H). 13C NMR (DMSO-d6): δ = 170.97, 169.60,
153.47, 148.62, 140.92, 131.31, 121.28, 115.90, 115.34, 36.55,
32.59, 28.73, 25.39. C15H19F3N2O3. MS (ESIþ) m/z 332.1348
(100%, (M þ Hþ)).
Compound 1r. Yellow oil crystallizing on standing: mp = 132
ꢀC. 1H NMR (DMSO-d6): δ = 9.97 (s, 1H), 7.95-7.25 (m, 9H),
3.89 (s, 2H), 2.52-1.29 (m, 12H). 13C NMR (DMSO-d6): δ =
171.66, 168.58, 144.06, 143.11, 141.38, 138.73, 136.46, 127.07,
126.38, 125.35, 120.38, 119.72, 118.25, 116.28, 36.84, 32.60,
28.76, 25.45, 25.40. C21H24N2O3. MS (ESIþ) m/z 352.1787
(100%, (M þ Hþ)).
Compound 1s. Gray solid: mp = 158 ꢀC. 1H NMR (DMSO-
d6):δ=10.31 (s, 1H), 8.33-7.38 (m, 10H), 6.35 (s, 1H), 2.62-1.40
(m, 12H). 13C NMR (DMSO-d6): δ = 170.23, 167.29, 142.44,
130.10, 130.06, 129.75, 128.90, 128.56, 126.19, 125.77, 125.29,
124.41, 123.93, 122.92, 120.98, 120.43, 119.82, 112.78, 111.19,
34.03, 30.38, 26.62, 26.54, 23.37, 23.19. C24H24N2O3. MS (ESIþ)
m/z 388.1787 (100%, (M þ Hþ)).
Compound 1g. Yellow oil crystallizing on standing: mp = 64
ꢀC. 1H NMR (DMSO-d6): δ = 10.26 (s, 1H), 7.79-7.62 (m, 4H),
2.51-1.26 (m, 14H). 13C NMR (DMSO-d6): δ = 172.36, 169.59,
143.17, 126.27, 119.22, 36.74, 32.57, 28.69, 25.35, 24.62.
C15H19F3N2O3. MS (ESIþ) m/z 332.1348 (100%, (M þ Hþ)).
Compound 1h. White solid: mp = 146 ꢀC. 1H NMR (DMSO-
d6): δ = 10.01 (s, 1H), 7.64-7.32 (m, 4H), 2.51-1.27 (m, 14H).
13C NMR (DMSO-d6): δ = 171.75, 169.46, 138.64, 128.89,
126.78, 120.89, 36.70, 32.59, 28.74, 25.38, 25.29, 24.79.
C14H19ClN2O3. MS (ESIþ) m/z 298.1084 (100%, (M þ Hþ)).
Compound 1i. Yellow solid: mp = 140 ꢀC. 1H NMR (DMSO-
d6): δ = 10.08 (s, 1H), 7.80 (s, 1H), 7.40-7.26 (m, 2H), 7.07-
7.03 (m, 1H), 2.31-2.26 (m, 2H), 1.98-1.93 (m, 2H), 1.57-
1.22 (m, 10H). 13C NMR (DMSO-d6): δ = 172.24, 169.77,
140.97, 133.37, 130.66, 123.05, 118.91, 117.79, 36.67, 32.56,
28.64, 25.33. C14H19ClN2O3. MS (ESIþ) m/z 298.1084 (100%,
(M þ Hþ)).
Compound 1t. White solid: mp = 164 ꢀC. 1H NMR (DMSO-
d6): δ = 2.51(s, 1H), 1.96-1.91 (m, 5H), 1.47-1.19 (m, 11H). 13
C
NMR (DMSO-d6): δ = 169.78, 32.54,28.54, 25.32. C8H16-
N2O4. MS (ESIþ) m/z 204.1110 (100%, (M þ Hþ)).
Compound 1u. White solid: mp = 126 ꢀC. 1H NMR (DMSO-
d6): δ = 3.16 (s, 2H), 2.03-1.92 (m, 4H), 1.43-1.27 (m, 9H). 13
C
NMR (DMSO-d6): δ = 180.63, 170.40, 48.90, 37.01, 32.50,
29.16, 28.91, 28.59, 25.88, 25.32. C8H15NO4. MS (ESIþ) m/z
189.1001 (100%, (M þ Hþ)).
Compound 1v. Yellow oil crystallizing on standing: mp =
62 ꢀC. 1H NMR (DMSO-d6): δ = 7.71-7.14 (m, 4H), 2.62-1.20
(m, 12H). 13C NMR (DMSO-d6): δ = 176.91, 167.79, 141.38,
125.57, 121.43, 121.26, 116.53, 109.73, 47.05, 30.65, 26.69, 23.44.
C12H17FN4O4. MS (ESIþ) m/z 300.2932 (100%, (M þ Hþ)).
Cell Culture Conditions and Proliferation Assay. The human
breast cancer cell line SKBR3 and colon adenocarcinoma cell
line HT29 were cultured in Dulbecco’s modified Eagle’s medium
(DMEM) supplemented with 10% fetal bovine serum (FBS) and
0.1% sodium pyruvate. The human U937 and HL60 myeloid
leukemia cell lines, K562 chronic erythromyeloid leukemia
cells, and clone Jurkat leukemia JA16 cells were maintained in
RPMI-1640 medium supplemented with 10% FBS at 37 ꢀC
with 5% CO2. Peripheral blood mononuclear cells (PBMCs)
were obtained from donors whole blood cells and cultured in
RPMI-1640 medium supplemented with 10% FBS at 37 ꢀC with
5% CO2.
Compound 1j. Brown solid: mp = 68 ꢀC. 1H NMR (DMSO-
d6): δ = 9.41 (s, 1H), 7.67-7.11 (m, 4H), 2.56-1.27(m, 14H). 13
C
NMR (DMSO-d6): δ = 171.81, 169.49, 136.76, 132.94, 128.27,
127.31, 118.57, 35.99, 32.62, 28.73, 25.45. C14H19BrN2O3. MS
(ESIþ) m/z 342.0579 (100%, (M þ Hþ)).
Compound 1k. White solid: mp = 150 ꢀC. 1H NMR (DMSO-
d6): δ = 9.99 (s, 1H), 7.62-7.41 (m, 4H), 2.52-2.51 (m, 2H),
2.30-2.25 (m, 2H), 1.96-1.92 (m, 2H), 1.58-1.25 (m, 8H). 13
C
NMR (DMSO-d6): δ = 171.92, 169.61, 139.43, 137.64, 121.66,
86.62, 36.73, 32.57, 28.69, 25.35, 26.26. C14H19IN2O3. MS
(ESIþ) m/z 390.0440 (100%, (M þ Hþ)).
1
Compound 1l. Pale-yellow oil: H NMR (DMSO-d6): δ =
9.780 (s, 1H), 7.38-6.94 (m, 4H), 2.52-2.50 (m, 1H), 2.25-1.22
(m, 13H). 13C NMR (DMSO-d6): δ = 180.28, 170.60, 152.71,
150.46, 127.36, 126.85, 121.50, 119.64, 114.27, 37.34, 33.20,