6094
P. Zhang et al. / European Journal of Medicinal Chemistry 46 (2011) 6089e6097
4
.3. General procedure for compounds (15e25)
J ¼ 2.7 Hz, 1H), 9.23 (s, 1H), 8.56e8.55 (m, 1H), 8.49 (d, J ¼ 5.0 Hz,
H), 8.30 (d, J ¼ 4.6 Hz, 1H), 7.65 (d, J ¼ 8.7 Hz, 1H), 7.59e7.58 (m,
1
13
To a stirred solution of -tryptophan 13 or 5-Hydroxy-
L
L-trypto-
2H), 7.29e7.28 (m, 2H), 7.12 (dd, J ¼ 2.3 Hz and 8.7 Hz,1H); C NMR
(DMSO-d , 151 MHz) (ppm): 187.4, 151.3, 138.2, 137.7, 136.1, 135.9,
135.6, 135.5, 130.5, 127.2, 122.8, 122.0, 121.6, 120.7, 118.6, 117.9, 114.2,
phan 14 (2.6 mmol) and p-toluenesulfonic acid (2.6 mmol) in
absolute methanol (30 mL), was added appropriated indole-3-
glyoxal 9e12 (2 mmol). The resulting solution was stirred at
5
6
d
ꢁ1
113.5, 112.3, 105.6; IR (KBr, cm ): 3421, 3269, 3236, 1609, 1564,
ꢀ
þ
0
C for 2 h. TLC showed that the reaction was completed. The
1429, 1230, 1125, 751; HRMS: m/z calcd. for C20
H
14
N
3
O
2
, 328.1086;
reaction mixture was poured into water and the precipitate was
filtered and purified by flash chromatography on silica gel (PE/
acetone) to afford the desired compounds 15e25.
found: 328.1076.
4.3.6. (5-Bromo-1H-indol-3-yl)-(6-hydroxy-9H-pyrido[3,4-b]
indol-1-yl)-methan- one (20)
ꢀ
1
4
.3.1. (1H-indol-3-yl)-(9H-pyrido[3,4-b]indol-1-yl)-met-hanone (15)
Yield, 20%; orange powder; mp 313e315 C; H NMR (DMSO-d6,
600 MHz)
ꢀ
1
Yield, 27%; pale yellow powder; mp 229e231 C; H NMR (CD
00 MHz)
H), 8.60e8.59 (m,1H), 8.58 (d, J ¼ 4.7 Hz,1H), 8.27 (dd, J ¼ 0.8 Hz and
.7 Hz,1H), 8.26 (dd, J ¼ 0.8 Hz and 7.7 Hz,1H), 7.77 (d, J ¼ 8.5 Hz,1H),
3
CN,
d
(ppm): 12.28 (d, J ¼ 1.6 Hz, 1H), 11.75 (s, 1H), 9.32 (d,
6
1
4
d
(ppm): 10.98 (brs, 1H), 10.15 (brs, 1H), 9.40 (d, J ¼ 3.3 Hz,
J ¼ 3.3 Hz, 1H), 9.24 (s,1H), 8.74 (d, J ¼ 1.6 Hz, 1H), 8.50 (d, J ¼ 4.9 Hz,
1H), 8.32 (d, J ¼ 4.9 Hz, 1H), 7.65 (d, J ¼ 8.8 Hz, 1H), 7.59 (d, J ¼ 2.2 Hz,
1H), 7.56 (d, J ¼ 8.8 Hz,1H), 7.43e7.42 (m,1H), 7.13 (dd, J ¼ 2.2 Hz and
13
13
7.63e7.62 (m, 1H), 7.56e7.55 (m, 1H), 7.33e7.32 (m, 3H); C NMR
8.8 Hz, 1H); C NMR (DMSO-d
6
,151 MHz)
d
(ppm): 187.3, 151.4, 138.6,
(
1
1
7
CD
3
CN, 151 MHz)
d
(ppm): 189.4, 142.4, 139.5, 138.7, 138.4, 137.1, 136.9,
137.7, 136.2, 135.6, 135.6, 134.7, 130.6, 129.1, 125.3, 124.0, 120.7, 118.7,
118.3,114.8,114.3,113.7,113.5,105.7; IR (KBr, cm ): 3438, 3303, 3152,
ꢁ1
32.1, 129.9, 128.5, 124.2, 123.3, 123.1, 121.7, 121.3, 118.9, 118.3, 115.8,
13.4, 112.9; IR (KBr, cm ): 3412, 3225, 1597, 1555, 1443, 1232, 1137,
36; HRMS: m/z calcd. for C20
ꢁ
1
1604, 1511, 1424, 1230, 1130, 757, 721, 667; HRMS: m/z calcd. for
þ
þ
H
14
N
3
O , 312.1137; found: 312.1132.
C
20
H
13
N
3
O
2
Br , 406.0191; found: 406.0187.
4.3.2. (5-Bromo-1H-indol-3-yl)-(9H-pyrido[3,4-b]indol-1-yl)-
4.3.7. (5-Nitro-1H-indol-3-yl)-(6-hydroxy-9H-pyrido[3, 4-b]indol-
methanone (16)
Yield, 27%; pale yellow powder; mp 266e268 C; 1H NMR
DMSO-d , 600 MHz) (ppm): 12.33 (s, 1H), 12.06 (s, 1H), 9.36 (d,
J ¼ 2.7 Hz, 1H), 8.78 (d, J ¼ 1.9 Hz, 1H), 8.60 (d, J ¼ 5.0 Hz, 1H), 8.44
d, J ¼ 4.6 Hz, 1H), 8.33 (d, J ¼ 7.8 Hz, 1H), 7.87 (d, J ¼ 8.2 Hz, 1H),
.63e7.62 (m, 1H), 7.59 (d, J ¼ 8.2 Hz, 1H), 7.45e7.44 (m, 1H),
.33e7.32 (m,1H); 13C NMR (DMSO-d
, 151 MHz) (ppm): 187.2,
41.6, 138.7, 137.9, 137.1, 135.1, 134.7, 130.9, 129.1, 128.8, 125.4, 123.9,
1-yl)-methanone (21)
ꢀ
Yield, 23%; deep yellow powder; mp 336e338 C; 1H NMR
ꢀ
(
6
d
6
(DMSO-d , 600 MHz) d(ppm): 12.68 (brs, 1H), 11.87 (s, 1H), 9.53 (s,
1H), 9.52 (d, J ¼ 2.5 Hz, 1H), 9.27 (s, 1H), 8.53 (d, J ¼ 4.7 Hz, 1H), 8.36
(
7
7
1
(d, J ¼ 5.1 Hz, 1H), 8.20 (dd, J ¼ 2.2 Hz and 8.8 Hz, 1H), 7.79 (d,
J ¼ 8.8 Hz, 1H), 7.67 (d, J ¼ 8.8 Hz, 1H), 7.60 (d, J ¼ 2.2 Hz, 1H), 7.14
13
6
d
(dd, J ¼ 2.2 Hz and 8.8 Hz, 1H); C NMR (DMSO-d
6
, 151 MHz)
d(ppm): 187.2, 151.4, 142.8, 140.5, 139.0, 137.2, 136.3, 135.6, 135.6,
ꢁ
1
121.7, 120.0, 119.9, 118.2, 114.9, 114.4, 113.7, 113.0; IR (KBr, cm ):
130.7, 126.6, 120.6, 118.7, 118.5, 118.2, 115.4, 113.5, 112.9, 105.7; IR
ꢁ
1
3
408, 3152, 1603, 1513, 1431, 1213, 1136, 743, 718, 669; HRMS: m/z
(KBr, cm ): 3416, 3323, 3167, 1613, 1536, 1460, 1339, 1145, 738;
þ
þ
calcd. for C20
13
H N
3
OBr , 390.0242; found: 390.0252.
HRMS: m/z calcd. for C20
13
H N
4
O
4
, 373.0937; found: 373.0936.
4
.3.3. (5-Nitro-1H-indol-3-yl)-(9H-pyrido[3,4-b]indol-1-yl)-
methanone (17)
Yield, 25%; pale yellow powder; mp 324e326 C; 1H NMR
DMSO-d , 600 MHz) (ppm): 12.72 (brs, 1H), 12.15 (s, 1H),
.53e9.52 (m, 2H), 8.62 (d, J ¼ 5.0 Hz, 1H), 8.48 (d, J ¼ 4.6 Hz, 1H),
.35 (d, J ¼ 8.7 Hz, 1H), 8.20 (dd, J ¼ 2.3 Hz and 8.7 Hz, 1H), 7.86 (d,
4.3.8. (5-Methoxy-1H-indol-3-yl)-(6-hydroxy-9H-pyrido [3,4-b]
indol-1-yl)-meth- anone (22)
ꢀ
ꢀ
1
Yield, 21%; yellow powder; mp 277e279 C; H NMR (DMSO-d6,
600 MHz)
(
9
8
6
d
d
(ppm): 12.00 (d, J ¼ 2.6 Hz, 1H), 11.75 (s, 1H), 9.24 (d,
J ¼ 3.3 Hz,1H), 9.22 (s, 1H), 8.48 (d, J ¼ 5.1 Hz,1H), 8.29 (d, J ¼ 4.7 Hz,
1H), 8.11 (d, J ¼ 2.6 Hz, 1H), 7.66 (d, J ¼ 8.8 Hz,1H), 7.58 (d, J ¼ 2.2 Hz,
J ¼ 8.2 Hz, 1H), 7.79 (d, J ¼ 8.7 Hz, 1H), 7.63e7.62 (m, 1H), 7.34e7.33
m, 1H); 13C NMR (DMSO-d
, 151 MHz) (ppm): 187.2, 142.9, 141.8,
40.8, 139.2, 137.4, 137.1, 135.2, 131.1, 128.9, 126.7, 121.8, 120.1, 120.0,
1H), 7.47 (d, J ¼ 8.8 Hz, 1H), 7.11 (dd, J ¼ 2.2 Hz and 8.8 Hz, 1H),
13
(
1
6
d
6.91e6.90 (m, 1H), 3.86e3.85 (m, 3H); C NMR (DMSO-d
6
, 151 MHz)
d(ppm): 187.3,155.6,151.3,138.3,137.8,136.1,135.6,135.5,130.7,130.5,
ꢁ
1
1
1
18.6, 118.3, 118.2, 115.5, 113.1, 113.1; IR (KBr, cm ): 3416, 3152,
606, 1523, 1456, 1424, 1333, 1147, 739; HRMS: m/z calcd. for
128.1, 120.7, 118.6, 117.9, 114.2, 113.6, 112.9, 112.7, 105.6, 103.3, 55.2; IR
ꢁ1
(KBr, cm ): 3463, 3194, 2914, 2821, 1611, 1521, 1421, 1268, 1142, 771,
þ
þ
C
H
20 13
N
4
O
3
, 357.0988; found: 357.0978.
746; HRMS: m/z calcd. for C21
H
16
N
3
O
3
, 358.1192; found: 358.1194.
4
.3.4. (5-Methoxy-1H-indol-3-yl)-(9H-pyrido[3,4-b]indol-1-yl)-
methanone (18)
Yield, 27%; pale yellow powder; mp 214e216 C; 1H NMR
DMSO-d , 600 MHz)
(ppm): 12.04 (s, 2H), 9.25 (d, J ¼ 3.3 Hz, 1H),
4.3.9. 1-(1H-indol-3-ylcarbonyl)-9H-pyrido[3,4-b]indo- le-3-
carboxylic acid (23)
ꢀ
Yield, 23%; pale yellow powder; mp 256e258 C; 1H NMR
ꢀ
(
6
d
6
(DMSO-d , 600 MHz) d(ppm): 13.17 (brs, 1H), 12.42 (s, 1H), 12.28 (s,
8
1
1
3
.57 (d, J ¼ 4.9 Hz, 1H), 8.41 (d, J ¼ 4.9 Hz, 1H), 8.32 (d, J ¼ 7.7 Hz,
1H), 9.76 (d, J ¼ 3.2 Hz, 1H), 9.15 (s, 1H), 8.61e8.60 (m, 1H), 8.48 (d,
H), 8.12 (d, J ¼ 2.2 Hz, 1H), 7.86 (d, J ¼ 8.3 Hz, 1H), 7.61 (t, J ¼ 7.7 Hz,
H), 7.48 (d, J ¼ 8.8 Hz, 1H), 7.31e7.30 (m, 1H), 6.92e6.91 (m, 1H),
J ¼ 7.8 Hz, 1H), 7.91 (d, J ¼ 8.2 Hz, 1H), 7.66e7.65 (m, 1H), 7.58e7.57
13
6
(m, 1H), 7.38e7.37 (m, 1H), 7.32e7.30 (m, 2H); C NMR (DMSO-d ,
.86 (s, 3H); 13C NMR (DMSO-d
, 151 MHz)
d(ppm): 187.2, 155.6,
151 MHz)
d(ppm): 186.4, 166.8, 142.1, 138.4, 137.1, 135.9, 135.8, 131.3,
6
1
41.6, 138.5, 137.9, 136.9, 135.0, 130.7, 130.7, 128.6, 128.0, 121.6,
129.1, 127.3, 123.0, 122.2, 122.1, 121.7, 120.7, 120.5, 119.9, 114.2, 113.4,
ꢁ
1
120.0, 119.8, 117.9, 114.1, 113.0, 113.0, 112.7, 103.3, 55.2; IR (KBr,
112.3; IR (KBr, cm ): 3410, 3269, 3241, 3213, 1704, 1599, 1498,
ꢁ
1
ꢁ
cm ): 3412, 3157, 2925, 2854, 1602, 1511, 1474, 1212, 1140, 739;
HRMS: m/z calcd. for C21
1429, 1241, 1163, 737; HRMS: m/z calcd. for C21
H
12
N
3
O
3
, 354.0879;
þ
H
16
N
3
O
2
, 342.1243; found: 342.1238.
found: 354.0896.
4
.3.5. (1H-indol-3-yl)-(6-hydroxy-9H-pyrido[3,4-b]indol-1-yl)-
methanone (19)
Yield, 29%; deep yellow powder; mp 324e326 C; 1H NMR
DMSO-d , 600 MHz) (ppm): 12.11 (s,1H), 11.73 (s, 1H), 9.26 (d,
4.3.10. 1-(5-Methoxy-1H-indol-3-ylcarbonyl)-9H-pyrido [3,4-b]
indole-3-carboxyl- ic acid (24)
ꢀ
Yield, 26%; pale yellow powder; mp 218e220 C; 1H NMR
ꢀ
(
6
d
(DMSO-d6, 600 MHz) d(ppm): 13.14 (brs, 1H), 12.43 (s, 1H), 12.17 (d,