H.-K. Rhee et al. / European Journal of Medicinal Chemistry 46 (2011) 3900e3908
3905
13C NMR (100 MHz, CDCl3)
d
168.38, 162.16 (2C, carbonyl), 151.61
4.6.14. 2-(4-(4-(Naphthalen-1-ylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5n)
White solid, 23% (18 mg), mp 257e260 ꢀC; 1H NMR (400 MHz,
CDCl3)
(1C, quinazoline), 148.58, 137.90, 136.67, 136.64, 133.69, 131.62,
131.27, 130.31, 130.16, 129.98, 127.84(two overlapping signals),
127.56, 126.27(two overlapping signals), 126.80, 125.84, 123.85
(18C, aromatic), 121.06(1C, eCF3), 46.37, 45.52 (4C, piperazine). HR-
FABMS Calcd for C26H22O4N4F3S (MþþH): 543.1314, Found:
543.1316.
d
10.840 (s, 1H), 8.741 (d, J ¼ 8.8 Hz, 1H), 8.312 (d, J ¼ 8.0 Hz,
1H), 8.243 (d, J ¼ 7.4 Hz, 1H), 8.206 (d, J ¼ 8.4 Hz, 2H), 8.138 (t,
J ¼ 7.2 Hz, 1H), 7.984 (t, J ¼ 7.0 Hz, 1H), 7.844 (d, J ¼ 6.8 Hz, 2H),
7.696 (t, J ¼ 7.7 Hz, 1H), 7.648 (t, J ¼ 7.2 Hz, 1H), 7.602 (t, J ¼ 6.5 Hz,
1H), 7.549 (t, J ¼ 4.0 Hz, 1H), 7.521 (d, J ¼ 9.6 Hz, 2H), 3.839e3.178
4.6.10. 2-(4-(4-(2-(Trifluoromethyl)phenylsulfonyl)piperazine-1-
carbonyl)phenyl) quinazolin-4(3H)-one (5j)
(m, 8H). 13C NMR (100 MHz, CDCl3)
d 169.39, 163.48 (2C, carbonyl)
150.52 (1C, quinazoline), 149.20, 137.81, 136.61, 135.12, 134.99,
134.46, 134.38, 132.10, 130.89, 129.14, 128.88, 128.42, 128.15, 127.81,
127.66, 127.36, 127.31, 127.11, 126.45, 124.86, 124.23, 120.95 (22C,
aromatic), 45.60 (4C, piperazine). IR (film) 3074, 2921, 2854, 1664,
1632, 1438, 1284, 1161, 1131, 932, 767 cmꢂ1. HR-FABMS Calcd for
C29H25O4N4S (MþþH): 525.1597, Found: 525.1594.
Pale brown solid, 15% (12 mg), mp 269e271 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
10.658 (s, 1H), 8.336 (d, J ¼ 8.0 Hz, 1H), 8.231 (d,
J ¼ 8.4 Hz, 2H), 8.176e8.153 (m, 1H), 7.947e7.914 (m, 1H),
7.839e7.826 (m, 2H), 7.771e7.726 (m, 2H), 7.591 (d, J ¼ 8.4 Hz, 2H),
7.561e7.534 (m, 1H), 3.870e3.317 (m, 8H). 13C NMR (100 MHz,
CDCl3)
d 169.57, 163.75 (2C, carbonyl), 150.63 (1C, quinazoline),
149.28, 137.82, 137.15, 135.14, 134.48, 133.17, 133.17, 132.38, 132.25,
128.85, 128.78, 128.37, 128.17, 128.04, 127.80, 127.46, 127.30, 126.43
(18C, aromatic), 120.95 (1C, CF3), 45.58, (4C, piperazine). IR (film)
3062, 2923, 1662, 1622, 1599, 1435, 1283, 1144, 1118, 1007, 942, 856,
766 cmꢂ1. HR-FABMS Calcd for C26H22O4N4F3S (MþþH): 513.1314,
Found: 543.1318.
4.6.15. 2-(4-(4-(Naphthalen-2-ylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5o)
Pale pink solid, 29% (23 mg), mp 217e220 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
10.967 (s, 1H), 8.346 (s, 1H), 8.303 (d, J ¼ 8.0 Hz,
1H), 8.209 (d, J ¼ 8.0 Hz, 2H), 8.031 (t, J ¼ 8.0 Hz, 2H), 7.973 (d,
J ¼ 7.6 Hz, 1H), 7.824 (d, J ¼ 3.6 Hz, 2H), 7.758 (d, J ¼ 8.6 Hz, 1H),
7.725 (t, J ¼ 7.5 Hz, 1H), 7.679 (t, J ¼ 7.5Hz, 1H), 7.531e7.490 (m, 3H),
4.6.11. 2-(4-(4-(Benzylsulfonyl)piperazine-1-carbonyl)phenyl)
quinazolin-4(3H)-one (5k)
3.912e3.074 (m, 8H). 13C NMR (100 MHz, CDCl3)
d 169.39, 163.64,
(2C, carbonyl) 150.57 (1C, quinazoline), 149.23, 137.72, 135.10,
134.41, 132.55, 132.26, 129.60, 129.32, 129.23, 129.20, 128.14, 128.03,
127.87(two overlapping signals), 127.81(two overlapping signals),
127.72(two overlapping signals), 127.28, 126.41, 122.74, 120.92 (22C,
aromatic), 46.09 (4C, piperazine). IR(film) 2924, 2854, 1658, 1622,
1460, 1434, 1283, 1158, 1011, 943, 855, 762, 717 cmꢂ1. HR-FABMS
Calcd for C29H25O4N4S (MþþH): 525.1597, Found: 525.1599.
Pale brown solid, 27% (20 mg), mp 177e178 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
10.326 (s, 1H), 8.340 (d, J ¼ 7.6 Hz, 1H), 8.191 (d,
J ¼ 7.6 Hz, 2H), 7.842 (d, J ¼ 4.6 Hz, 2H), 7.566 (t, J ¼ 8.2 Hz, 1H),
7.557 (d, J ¼ 7.4 Hz, 2H), 7.463e7.411 (m, 5H), 4.269 (s, 2H),
3.769e3.045 (m, 8H). 13C NMR (100 MHz, CDCl3)
d 169.44, 163.18
(2C, carbonyl), 150.41(1C, quinazoline), 149.17, 137.97, 135.15,
134.39, 130.66, 129.14, 128.97(two overlapping signals), 128.44(two
overlapping signals), 128.17, 127.82(two overlapping signals),
127.59(two overlapping signals), 127.36, 126.49, 121.01 (18C,
aromatic), 57.72 (1C, -NeCH2ePh), 45.93 (4C, piperazine). IR (film)
3062, 2923, 1669, 1597, 1438, 1144,942, 765, 707 cmꢂ1. HR-FABMS
Calcd for C26H25O4N4S (MþþH): 489.1597, Found: 489.1594.
4.6.16. 2-(4-(4-(Quinolin-8-ylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5p)
White solid, 21% (17 mg), mp 274e276 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
10.583 (s, 1H), 9.069 (d, J ¼ 4.4 Hz, 1H), 8.515 (d, J ¼ 7.4 Hz,
1H), 8.326 (d, J ¼ 7.6 Hz, 1H), 8.287 (d, J ¼ 8.4 Hz, 1H), 8.192 (d,
J ¼ 8.4 Hz, 2H), 8.086 (d, J ¼ 8.4 Hz, 1H), 7.833 (d, J ¼ 4.0 Hz, 2H),
7.669 (t, J ¼ 7.8 Hz, 1H), 7.581e7.527 (m, 4H), 3.881e3.492 (m, 8H).
4.6.12. 2-(4-(4-(4-Methylbenzylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5l)
13C NMR (100 MHz, CDCl3)
d 169.47, 163.50 (2C, carbonyl), 151.30
Pale yellow solid,13% (10 mg), mp 190e193 ꢀC; 1H NMR
(1C, quinazoline), 150.61, 149.23, 144.10, 138.15, 136.59, 135.61,
135.12, 134.27, 133.82, 133.28(two overlapping signals), 129.09,
128.54, 128.14, 127.81(two overlapping signals), 127.66(two over-
lapping signals), 127.29, 126.45, 125.63, 122.25, 120.95 (23C,
aromatic). HR-FABMS Calcd for C28H24O4N5S (MþþH): 526.1549,
Found: 526.1552.
(400 MHz, CDCl3)
d
10.058 (s, 1H), 8.341 (d, J ¼ 7.8 Hz, 1H), 8.160 (d,
J ¼ 8.4 Hz, 2H), 7.841 (d, J ¼ 4.4 Hz, 2H), 7.565e7.520 (m, 3H),
7.293e7.174 (m, 4H), 4.227 (s, 2H), 3.768e3.030 (m, 8H), 2.385 (s,
3H). 13C NMR (100 MHz, CDCl3)
d 169.49, 163.59 (2C, carbonyl),
150.57, (1C, quinazoline), 149.24, 139.14, 137.95, 135.15, 134.40,
130.51(two overlapping signals), 129.66(two overlapping signals),
128.16, 127.77, 127.74(two overlapping signals), 127.33, 126.45,
125.28, 122.99, 120.94, (18C, aromatic), 57.37 (1C, SO2-CH2- ), 46.13
(4C, piperazine), 21.28 (1C, eCH3). HR-FABMS Calcd for
C27H27O4N4S (MþþH): 503.1753, Found: 503.1756.
4.6.17. 2-(4-(4-(Thiophen-2-ylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5q)
Pale brown solid, 15% (22 mg), mp 194e197 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
11.198 (s, 1H), 8.330 (d, J ¼ 7.6 Hz, 1H), 8.279 (d,
J ¼ 8.8 Hz, 2H), 7.842 (d, J ¼ 4.6 Hz, 2H), 7.693 (d, J ¼ 5.2 Hz, 1H),
7.572e7.545(m, 4H), 7.208(t, J ¼ 4.4 Hz, 1H), 3.949e3.803(m, 8H).
4.6.13. 2-(4-(4-(4-Chlorobenzylsulfonyl)piperazine-1-carbonyl)
phenyl)quinazolin-4(3H)-one (5m)
13C NMR (100 MHz, CDCl3)
d 169.49, 169.33 (2C, carbonyl), 163.82
Pale yellow solid, 17% (13 mg), mp 210e214 ꢀC; 1H NMR
(1C, quinazoline), 150.65, 149.28, 137.67, 135.64, 135.13, 134.50,
132.91, 132.76, 128.16, 127.95, 127.85, 127.80, 127.46, 127.28, 126.40,
120.92, (16C, aromatic), 46.03 (4C, piperazine). IR (film) 3074, 2923,
2854, 1659, 1624, 1432, 1350, 1283, 1156, 1008, 939, 726 cmꢂ1. HR-
FABMS Calcd for C23H21O4N4S2 (MþþH): 481.1004, Found:
481.1005.
(400 MHz, CDCl3)
d
10.881 (s, 1H), 8.342 (d, J ¼ 8.0 Hz, 1H), 8.258 (d,
J ¼ 8.4 Hz, 2H), 7.846 (d, J ¼ 3.6 Hz, 2H), 7.582e7.530 (m, 3H),
7.406e7.332 (m, 4H), 4.213 (s, 2H), 3.794e3.079 (m, 8H). 13C NMR
(100 MHz, CDCl3)
d 169.54, 163.53, (2C, carbonyl), 150.52(1C, qui-
nazoline),149.22,138.88,1387.79,135.35,135.16,134.49,131.93(two
overlapping signals), 129.24(two overlapping signals), 127.80(two
overlapping signals), 127.35(two overlapping signals), 126.90,
126.45, 120.96, 95.01, (18C, aromatic), 56.94(1C, SO2-CH2-). HR-
FABMS Calcd for C26H24O4N4ClS (MþþH): 523.1207, Found:
523.1211.
4.6.18. 2-(4-(4-(Methylsulfonyl)piperazine-1-carbonyl)phenyl)
quinazolin-4(3H)-one (5r)
Pale brown solid, 11% (7 mg), mp 221e223 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
10.567 (s, 1H), 8.349 (d, J ¼ 7.2 Hz, 1H), 8.247 (d,