F.J. Scott et al. / European Journal of Medicinal Chemistry 116 (2016) 116e125
123
for C35H40N9O5 666.3152.
NMR (DMSO-d6): 10.80 (1H, s), 9.95 (1H, s), 9.44 (1H, s), 8.63 (1H, s),
8.29 (1H, d, J ¼ 8.0 Hz), 8.23 (1H, d, J ¼ 8.0 Hz), 8.15 (1H, t,
J ¼ 5.6 Hz), 7.91 (1H, t, J ¼ 7.2 Hz), 7.83 (1H, t, J ¼ 7.2 Hz), 7.43 (1H, s),
7.28 (1H, s), 7.19 (1H, s), 6.95 (1H, s), 3.85 (3H, s), 3.82 (3H, s), 3.26
(2H, q, J ¼ 6.0 Hz), 3.08 (2H, m), 2.80 (6H, d, J ¼ 4.8 Hz), 1.85 (2H,
quintet, J ¼ 8.0 Hz). IR (KBr): 1674, 1584, 1538, 1469, 1437, 1405,
1267, 1200, 1140 cmꢂ1. HRFABMS: found: 502.2566 calculated for
4.3.17. 4-{[(4-{[imino(3-methoxyphenyl)methyl]amino}-1-methyl-
1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-N-[1-methyl-5-({[3-(4-
morpholinyl)propyl]amino}carbonyl)-1H-pyrrol-3-yl]-1H-pyrrole-
2-carboxamide 9
Prepared as per [19].
C27H32O3N7 502.2567.
4.3.18. N-[3-(Dimethylamino)propyl]-5-isopentyl-2-({[1-methyl-4-
({4-[(E)-2-(3-quinolinyl)ethenyl]benzoyl}amino)-1H-pyrrol-2-yl]
carbonyl}amino)-1,3-thiazole-4-carboxamide 10
Prepared as per [19].
4.3.24. 4-({4-[(E)-2-(1,3-benzoxazol-2-yl)ethenyl]benzoyl}amino)-
1-methyl-N-[1-methyl-5-({[2-(4-morpholinyl)ethyl]amino}
carbonyl)-1H-pyrrol-3-yl]-1H-pyrrole-2-carboxamide 16
Yellow solid (6 mg, 7%) with no distinct melting point. 1H NMR
(DMSO-d6): 10.42 (1H, s), 9.98 (2H, s & br), 8.25 (1H, br), 8.03 (2H, d,
J ¼ 8.4 Hz), 7.97 (2H, d, J ¼ 8.4 Hz), 7.92 (1H, d, J ¼ 16.3 Hz), 7.76 (2H,
t, J ¼ 7.1 Hz), 7.50 (1H, d, J ¼ 16.3 Hz), 7.42 (2H, t, J ¼ 7.1 Hz), 7.35 (1H,
d, J ¼ 1.6 Hz), 7.22 (1H, d, J ¼ 1.6 Hz), 7.13 (1H, d, J ¼ 1.6 Hz), 6.99 (1H,
d, J ¼ 1.6 Hz), 4.02e3.99 (2H, m), 3.88 (3H, s), 3.83 (3H, s), 3.72e3.64
(2H, m), 3.55e3.54 (4H, m), 3.27 (2H, m), 3.14 (2H, m). IR (KBr):
3427, 1673, 1588, 1402, 1253, 1202, 1174, 832, 720 cmꢂ1. HRFABMS:
found: 622.2775 calculated for C34H36O5N7 622.2772.
4.3.19. N-[3-(dimethylamino)propyl]-5-isopentyl-2-({[4-({4-[(E)-
2-(3-methoxyphenyl)ethenyl]benzoyl}amino)-1-methyl-1H-pyrrol-
2-yl]carbonyl}amino)-1,3-thiazole-4-carboxamide 11
Prepared as per [19].
4.3.20. N-[3-(Dimethylamino)propyl]-5-isopentyl-2-({[4-({3-[(E)-
2-(3-methoxyphenyl)ethenyl]benzoyl}amino)-1-methyl-1H-pyrrol-
2-yl]carbonyl}amino)-1,3-thiazole-4-carboxamide 12
White solid (26 mg, 28%), with no distinct melting point. 1H
NMR (DMSO-d6): 12.13 (1H, s), 10.48 (1H, s), 9.51 (1H, br), 8.15 (1H,
br), 7.96 (1H, t, J ¼ 6.1 Hz), 7.84 (2H, q, J ¼ 7.8 Hz), 7.55 (2H, m), 7.45
(1H, d, J ¼ 1.7 Hz), 7.37e7.29 (3H, m), 7.23e7.21 (2H, m), 6.89e6.87
(1H, m), 3.93 (3H, s), 3.81 (3H, s), 3.36 (2H, t, J ¼ 6.5 Hz), 3.22 (2H, t,
J ¼ 7.7 Hz), 3.11e3.05 (2H, m), 2.79 (6H, d, J ¼ 4.8 Hz), 1.91(2H, t,
J ¼ 7.7 Hz), 1.63e1.50 (3H, m), 0.93 (6H, d, J ¼ 6.4 Hz). IR (KBr): IR
(KBr): 1682, 1641, 1583, 1540, 1464, 1435, 1404, 1266, 1202,
1134 cmꢂ1. HRFABMS: Found: 657.3226 Calculated for C36H45O4N6S
657.3218.
4.3.25. N-[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-
methyl-1H-pyrrol-3-yl]-4-{[(4-{[imino(3-isoquinolinyl)methyl]
amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-
pyrrole-2-carboxamide 17
Yellow solid (26 mg, 41%) with no distinct melting point. 1H
NMR (DMSO-d6): 10.02 (1H, s), 9.91 (1H, s), 9.60 (1H, s), 8.91 (1H, s),
8.40 (1H, d, J ¼ 8.1 Hz), 8.20 (1H, d, J ¼ 8.1 Hz), 8.03 (1H, t,
J ¼ 8.9 Hz), 7.98 (1H, t, J ¼ 8.9 Hz), 7.32 (1H, d, J ¼ 1.7 Hz), 7.26 (1H, d,
J ¼ 1.7 Hz), 7.16 (1H, d, J ¼ 1.7 Hz), 7.11 (1H, d, J ¼ 1.7 Hz), 7.08 (1H, d,
J ¼ 1.7 Hz), 6.95 (1H, d, J ¼ 1.7 Hz), 3.97 (3H, s), 3.86 (3H, s), 3.81 (3H,
s), 3.24 (2H, t, J ¼ 6.4 Hz), 3.07 (2H, m), 2.79 (6H, s), 1.84 (2H,
quintet, J ¼ 7.6 Hz). IR (KBr): 1675, 1582, 1545, 1467, 1436, 1405,
1263, 1202, 1134, 802, 720 cmꢂ1. HRFABMS: found: 623.3202
calculated for C33H39O3N10 623.3207.
4.3.21. N-[3-(dimethylamino)propyl]-5-isopentyl-2-[({1-methyl-4-
[({1-methyl-4-[(E)-2-(4-nitrophenyl)ethenyl]-1H-pyrrol-2-yl}
carbonyl)amino]-1H-pyrrol-2-yl}carbonyl)amino]-1,3-thiazole-4-
carboxamide 13
Orange solid (17 mg, 18%), with no distinct melting point. 1H
NMR (DMSO-d6): 12.09 (1H, s), 10.15 (1H, s), 9.41 (1H, br), 8.19 (2H,
d, J ¼ 8.9 Hz), 7.99 (1H, t, J ¼ 6.1 Hz), 7.76 (2H, d, J ¼ 8.9 Hz), 7.46 (1H,
d, J ¼ 1.7 Hz), 7.41 (2H, dd, J ¼ 1.7 Hz & d, J ¼ 16.2 Hz), 7.33 (1H, d,
J ¼ 1.7 Hz), 7.27 (1H, d, J ¼ 1.7 Hz), 6.96 (1H, d, J ¼ 16.2 Hz), 3.90 (6H,
s), 3.36 (2H, q, J ¼ 6.5 Hz), 3.21 (2H, t, J ¼ 7.7 Hz), 3.11e3.06 (2H, m),
2.79 (6H, d, J ¼ 4.8 Hz), 1.91 (2H, t, J ¼ 6.8 Hz), 1.63e1.49 (3H, m),
0.93 (6H, d, J ¼ 6.4 Hz). IR (KBr): 1680, 1645, 1580, 1544, 1461, 1440,
1414, 1269, 1206, 1133 cmꢂ1. HRFABMS: Found: 675.3082 Calcu-
lated for C34H43O5N8S 675.3072.
4.3.26. N-[5-({[4-({[3-(Dimethylamino)propyl]amino}carbonyl)-5-
isopentyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-
yl]-3-isoquinolinecarboxamide 18
Prepared as per [19].
4.3.27. N-[3-(Dimethylamino)propyl]-2-{[(4-{[(4-{[imino(3-
isoquinolinyl)methyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]
amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-5-isopentyl-1,3-
thiazole-4-carboxamide 19
Prepared as per [19].
4.3.22. N-[1-Methyl-5-({[1-methyl-5-({[2-(4-morpholinyl)ethyl]
amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-
3-isoquinolinecarboxamide 14
4.3.28. 5-isopentyl-2-({[1-methyl-4-({4-[(E)-2-(2-naphthyl)
ethenyl]benzoyl}amino)-1H-pyrrol-2-yl]carbonyl}amino)-N-[2-(4-
morpholinyl)ethyl]-1,3-thiazole-4-carboxamide 20
Prepared as per [19].
Yellow solid (85 mg, 54%) with no distinct melting point. 1H
NMR (DMSO-d6): 10.81 (1H, s), 9.98 (1H, s), 9.63 (1H, s), 9.44 (1H,
br), 8.63 (1H, s), 8.29 (1H, d, J ¼ 8.0 Hz), 8.24 (1H, d, J ¼ 8.0 Hz
overlapped with 1H broad), 7.92 (1H, t, J ¼ 7.2 Hz), 7.85 (1H, t,
J ¼ 7.2 Hz), 7.43 (1H, d, J ¼ 1.7 Hz), 7.30 (1H, d, J ¼ 1.7 Hz), 7.22 (1H, d,
J ¼ 1.7 Hz), 7.02 (1H, d, J ¼ 1.7 Hz), 4.03 (2H, m), 3.88 (3H, s), 3.83
(3H, s), 3.67 (2H, t, J ¼ 12.0 Hz), 3.05 (4H, m), 3.28 (2H, m), 3.13 (2H,
m). IR (KBr): 1672, 1584, 1539, 1463, 1436, 1405, 1268, 1201,
1136 cmꢂ1. HRFABMS: found: 530.2515 calculated for C28H32O4N7
530.2516.
4.3.29. 5-isopentyl-2-[({1-methyl-4-[({1-methyl-4-[(E)-2-(4-
nitrophenyl)ethenyl]-1H-pyrrol-2-yl}carbonyl)amino]-1H-pyrrol-2-
yl}carbonyl)amino]-N-[2-(4-morpholinyl)ethyl]-1,3-thiazole-4-
carboxamide 21
Prepared as per [22].
4.3.30. 1-methyl-N-[1-methyl-5-({[2-(4-morpholinyl)ethyl]amino}
carbonyl)-1H-pyrrol-3-yl]-4-[(4-{(E)-2-[4-(trifluoromethyl)phenyl]
ethenyl}benzoyl)amino]-1H-pyrrole-2-carboxamide 22
Pale yellow solid (29.6 mg, 32%) with no distinct melting point.
1H NMR (DMSO-d6): 10.38 (1H, s), 10.01 (1H, s), 9.65 (1H, br), 8.26
(1H, t, J ¼ 5.7 Hz), 8.01 (2H, d, J ¼ 8.5 Hz), 7.88 (2H, d, J ¼ 8.2 Hz),
4.3.23. N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-
methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-
3-isoquinolinecarboxamide 15
Yellow solid (88 mg, 54%) with no distinct melting point. 1H