242
A. Penta et al. / European Journal of Medicinal Chemistry 105 (2015) 238e244
128.85, 129.72, 129.88, 130.78, 131.93, 134.24, 138.99, 141.65, 142.41,
142.78, 150.98, 167.51; ESI-MS m/z 461 (M þ 1þ, 100%); Anal. Calcd
for C30H28N4O: C, 78.23; H, 6.13; N, 12.16, Found: C, 78.20; H, 6.12;
N, 12.18.
130e132 ꢁC; Rf 0.42 (Hexane: EtOAc ¼ 6:4); IR
n
max/cmꢀ1(KBr):
3069 (CeH, aromatic stretching), 1614 (C]O, stretching), 1534 (C]
C, aromatic stretching), 1487 (CeH, bending), 1054 (CeCl, stretch-
ing); 1H NMR (400 MHz, CDCl3)
d 8.95 (s, 1H, aromatic), 8.50 (s, 1H,
aromatic), 8.27-8.19 (m, 2H, aromatic), 7.69-7.60 (m, 5H, aromatic),
7.59-7.56 (m, 1H, aromatic), 7.51-7.48 (m, 1H, aromatic), 7.46-7.44
(m, 1H, aromatic), 7.42-6.86 (m, 2H, aromatic), 4.03 (m, 4H, piper-
azinyl (O]CN(CH2)2)), 3.54 (s, 3H, N-methyl), 3.38-3.25 (m, 4H,
piperazinyl (CN(CH2)2)); ESI-MS m/z 481 (M þ 1þ, 100%), 483
(M þ 3þ, 33%); Anal. Calcd for C29H25ClN4O: C, 72.42; H, 5.24; N,
11.65, Found: C, 72.46; H, 5.27; N, 11.68.
4.1.7.5. (4-(4-methoxyphenyl)piperazin-1-yl) (9-methyl-1-phenyl-
9H-pyrido[3,4-b]indol-3-yl)methanone (7e). White solid; Yield 82%;
mp 170e172 ꢁC; Rf 0.30 (Hexane: EtOAc ¼ 6:4); IR
nmax/
cmꢀ1(KBr): 3064 (CeH, aromatic stretching), 1651 (C]O, stretch-
ing), 1516 (C]C, aromatic stretching), 1454 (CeH, bending), 1255
(CeO, stretching); 1H NMR (400 MHz, CDCl3)
d 8.53 (s, 1H, aro-
matic), 8.21 (d, J ¼ 7.8 Hz,1H, aromatic), 7.66-7.62 (m, 4H, aromatic),
7.54-7.50 (m, 4H, aromatic), 7.45 (d, J ¼ 8.3 Hz, 1H, aromatic), 7.36 (t,
J ¼ 7.5 Hz, 1H, aromatic), 6.86 (d, J ¼ 8.8 Hz, 2H, aromatic), 4.10 (brs,
4H, piperazinyl (O]CN(CH2)2)), 3.77 (s, 3H, methoxy), 3.51 (s, 3H,
N-methyl), 3.25-3.17 (m, 4H, piperazinyl (CN(CH2)2)); ESI-MS m/z
477 (M þ 1þ, 100%); Anal. Calcd for C30H28N4O2: C, 75.61; H, 5.92; N,
11.76, Found: C, 75.65; H, 5.88; N, 11.71.
4.1.7.10. (4-(2-chlorophenyl)piperazin-1-yl) (9-methyl-1-phenyl-9H-
pyrido[3,4-b]indol-3-yl)methanone (7j). White solid; Yield 66%; mp
152e154 ꢁC; Rf 0.40 (Hexane: EtOAc ¼ 6:4); IR
n
max/cmꢀ1(KBr):
3043 (CeH, aromatic stretching), 1629 (C]O, stretching), 1556 (C]
C, aromatic stretching), 1435 (CeH, bending), 1068 (CeCl, stretch-
ing); 1H NMR (400 MHz, CDCl3)
d 8.51 (s, 1H, aromatic), 8.21 (d,
J ¼ 7.8 Hz, 1H, aromatic), 7.65-7.62 (m, 3H, aromatic), 7.56-7.44 (m,
4H, aromatic), 7.46-7.44 (m, 2H, aromatic), 7.24-7.20 (m, 1H, aro-
matic), 7.05-6.97 (m, 2H, aromatic), 4.04 (brs, 4H, piperazinyl (O]
CN(CH2)2)), 3.51 (s, 3H, N-methyl), 3.19-3.08 (m, 4H, piperazinyl
(CN(CH2)2)); ESI-MS m/z 481 (M þ 1þ, 100%), 483 (M þ 3þ, 33%);
Anal. Calcd for C29H25ClN4O: C, 72.42; H, 5.24; N, 11.65, Found: C,
72.40; H, 5.20; N, 11.64.
4.1.7.6. (4-(3-methoxyphenyl)piperazin-1-yl) (9-methyl-1-phenyl-
9H-pyrido[3,4-b]indol-3-yl)methanone (7f). White solid; Yield 74%;
mp 196e198 ꢁC; Rf 0.35 (Hexane: EtOAc ¼ 6:4); IR
nmax/
cmꢀ1(KBr): 3057 (CeH, aromatic stretching), 1625 (C]O, stretch-
ing), 1556 (C]C, aromatic stretching), 1454 (CeH, bending), 1253
(CeO, stretching); 1H NMR (400 MHz, CDCl3)
d 8.54 (s, 1H, aro-
matic), 8.21 (d, J ¼ 7.8 Hz,1H, aromatic), 7.66-7.62 (m, 3H, aromatic),
7.56-7.50 (m, 3H, aromatic), 7.46 (d, J ¼ 8.3 Hz, 1H, aromatic), 7.36 (t,
J ¼ 7.5 Hz, 1H, aromatic), 7.20 (t, J ¼ 8.0 Hz, 1H, aromatic), 6.62-6.48
(m, 3H, aromatic), 4.13-4.07 (m, 4H, piperazinyl (O]CN(CH2)2)),
3.80 (s, 3H, methoxy), 3.52 (s, 3H, N-methyl), 3.36-3.26 (m, 4H,
piperazinyl (CN(CH2)2)); ESI-MS m/z 477 (M þ 1þ, 100%); Anal.
Calcd for C30H28N4O2: C, 75.61; H, 5.92; N, 11.76, Found: C, 75.58; H,
5.94; N, 11.79.
4.1.7.11. (9-Methyl-1-phenyl-9H-pyrido[3,4-b]indol-3-yl) (4-(4-
nitrophenyl)piperazin-1-yl)methanone (7k). Yellow solid; Yield
70%; mp 200e202 ꢁC; Rf 0.30 (Hexane: EtOAc ¼ 6:4); IR
nmax/
cmꢀ1(KBr): 3053 (CeH, aromatic stretching), 1633 (C]O, stretch-
ing), 1597 (C]C, aromatic stretching), 1471 (CeH, bending), 1385
(NeO, stretching); 1H NMR (400 MHz, CDCl3)
d 8.61 (s, 1H, aro-
matic), 8.24 (d, J ¼ 7.8 Hz, 1H, aromatic), 8.15 (d, J ¼ 9.3 Hz, 2H,
aromatic), 7.70-7.63 (m, 3H, aromatic), 7.61-7.53 (m, 3H, aromatic),
7.49 (d, J ¼ 8.4 Hz, 1H, aromatic), 7.39 (t, J ¼ 7.5 Hz, 1H, aromatic),
6.83 (d, J ¼ 9.4 Hz, 2H, aromatic), 4.16-4.06 (m, 4H, piperazinyl (O]
CN(CH2)2)), 3.62-3.54 (m, 7H, piperazinyl (CN(CH2)2), N-methyl);
ESI-MS m/z 492 (M þ 1þ, 100%); Anal. Calcd for C29H25N5O3: C,
70.86; H, 5.13; N, 14.25, Found: C, 70.82; H, 5.12; N, 14.28.
4.1.7.7. (4-(2-methoxyphenyl)piperazin-1-yl) (9-methyl-1-phenyl-
9H-pyrido[3,4-b]indol-3-yl)methanone (7g). White solid; Yield 62%;
mp 168e170 ꢁC; Rf 0.35 (Hexane: EtOAc ¼ 6:4); IR
nmax/
cmꢀ1(KBr): 3058 (CeH, aromatic stretching), 1643 (C]O, stretch-
ing), 1536 (C]C, aromatic stretching), 1496 (CeH, bending), 1240
(CeO, stretching); 1H NMR (400 MHz, CDCl3)
d 8.54 (s, 1H, aro-
matic), 8.23 (d, J ¼ 7.8 Hz, 1H, aromatic), 7.68-7.64 (m, 3H, aro-
matic), 7.58-7.52 (m, 3H, aromatic), 7.48 (d, J ¼ 8.3 Hz,1H, aromatic),
7.38 (t, J ¼ 7.5 Hz, 1H, aromatic), 7.06-7.04 (m, 1H, aromatic), 6.96-
6.90 (m, 3H, aromatic), 4.08 (brs, 4H, piperazinyl (O]CN(CH2)2)),
3.90 (s, 3H, methoxy), 3.54 (s, 3H, N-methyl), 3.22-3.12 (m, 4H,
piperazinyl (CN(CH2)2)); ESI-MS m/z 477 (M þ 1þ, 100%); Anal.
Calcd for C30H28N4O2: C, 75.61; H, 5.92; N, 11.76, Found: C, 75.63; H,
5.97; N, 11.73.
4.1.7.12. (4-(4-fluorophenyl)piperazin-1-yl) (9-methyl-1-phenyl-9H-
pyrido[3,4-b]indol-3-yl)methanone (7l). White solid; Yield 76%; mp
188e190 ꢁC; Rf 0.40 (Hexane: EtOAc ¼ 6:4); IR
n
max/cmꢀ1(KBr):
3057 (CeH, aromatic stretching), 1614 (C]O, stretching), 1550 (C]
C, aromatic stretching), 1487 (CeH, bending), 1036 (CeF, stretch-
ing); 1H NMR (400 MHz, CDCl3)
d 8.56 (s, 1H, aromatic), 8.23 (d,
J ¼ 7.7 Hz, 1H, aromatic), 7.68-7.65 (m, 3H, aromatic), 7.58-7.53 (m,
3H, aromatic), 7.48 (d, J ¼ 8.4 Hz, 1H, aromatic), 7.38 (td, J ¼ 7.6,
0.8 Hz, 1H, aromatic), 7.06-6.96 (m, 2H, aromatic), 6.96-6.88 (m, 2H,
aromatic), 4.06-4.05 (m, 4H, piperazinyl (O]CN(CH2)2)), 3.54 (s,
3H, N-methyl), 3.26-3.16 (m, 4H, piperazinyl (CN(CH2)2)); ESI-MS
m/z 465 (M þ 1þ, 100%); Anal. Calcd for C29H25FN4O: C, 74.98; H,
5.42; N, 12.06, Found: C, 74.94; H, 5.45; N, 12.03.
4.1.7.8. (4-(4-chlorophenyl)piperazin-1-yl) (9-methyl-1-phenyl-9H-
pyrido[3,4-b]indol-3-yl)methanone (7h). White solid; Yield 76%; mp
160e162 ꢁC; Rf 0.40 (Hexane: EtOAc ¼ 6:4); IR
n
max/cmꢀ1(KBr):
3055 (CeH, aromatic stretching), 1633 (C]O, stretching), 1542 (C]
C, aromatic stretching), 1471 (CeH, bending), 1062 (CeCl, stretch-
ing); 1H NMR (400 MHz, CDCl3)
d
8.57 (s, 1H, aromatic), 8.24 (d,
4.1.7.13. (4-(2-fluorophenyl)piperazin-1-yl) (9-methyl-1-phenyl-9H-
pyrido[3,4-b]indol-3-yl)methanone (7m). White solid; Yield 68%;
J ¼ 7.8 Hz, 1H, aromatic), 7.68-7.64 (m, 3H, aromatic), 7.56-7.53 (m,
3H, aromatic), 7.50-7.48 (m, 1H, aromatic), 7.41-7.37 (m, 1H, aro-
matic), 7.26 (d, J ¼ 8.9 Hz, 2H, aromatic), 7.02-6.95 (m, 2H, aro-
matic), 4.10 (brs, 4H, piperazinyl (O]CN(CH2)2)), 3.54 (s, 3H, N-
methyl), 3.34-3.25 (m, 4H, piperazinyl (CN(CH2)2)); ESI-MS m/z 481
(M þ 1þ, 100%), 483 (M þ 3þ, 33%); Anal. Calcd for C29H25ClN4O: C,
72.42; H, 5.24; N, 11.65, Found: C, 72.39; H, 5.26; N, 11.63.
mp 168e170 ꢁC; Rf 0.45 (Hexane: EtOAc ¼ 6:4); IR
nmax/
cmꢀ1(KBr): 3055 (CeH, aromatic stretching), 1633 (C]O, stretch-
ing), 1544 (C]C, aromatic stretching), 1435 (CeH, bending), 1026
(CeF, stretching); 1H NMR (400 MHz, CDCl3)
d 8.53 (s, 1H, aro-
matic), 8.21 (d, J ¼ 7.8 Hz,1H, aromatic), 7.65-7.62 (m, 3H, aromatic),
7.55-7.50 (m, 3H, aromatic), 7.45 (d, J ¼ 8.3 Hz, 1H, aromatic), 7.36 (t,
J ¼ 7.5 Hz, 1H, aromatic), 7.07-6.93 (m, 4H, aromatic), 4.05-4.04 (m,
4H, piperazinyl (O]CN(CH2)2)), 3.51 (s, 3H, N-methyl), 3.23-3.13
(m, 4H, piperazinyl (CN(CH2)2)); ESI-MS m/z 465 (M þ 1þ, 100%);
4.1.7.9. (4-(3-chlorophenyl)piperazin-1-yl) (9-methyl-1-phenyl-9H-
pyrido[3,4-b]indol-3-yl)methanone (7i). White solid; Yield 70%; mp