M.-H. David-Cordonnier et al. / European Journal of Medicinal Chemistry 42 (2007) 752e771
765
6.87 (d, 1H, 4J ¼ 1.7 Hz, pyrrole-H-5), 7.17 (d, 1H,
(2t), 118.21 (t), 118.54 (t), 121.62 (2t), 121.91 (2q), 122.22
(q), 122.4 (q), 123.13 (2q), 127.07 (2t), 134.59 (2t), 141.87
(2q), 158.69 (q), 161.65 (q), 169.36 (q), 176.81 (q); FD-MS:
m/z 610 [Mþ], C34H39N7O4.
4
4J ¼ 1.8 Hz, pyrrole-H-30), 7.21 (d, 1H, J ¼ 1.6 Hz, pyrrole-
H-50), 7.35 (pt, 2H, 3J ¼ 7.0 Hz, acridone-H), 7.86 (m, 4H, ac-
ridone-H), 8.1 (t, 1H, 5.7 Hz, NH), 8.35 (m, 2H, acridone-H-
1 þ 8), 9.87 (s, 1H, NH), 10.07 (s, 1H, NH); 13C NMR
(DMSO-d6): d 26.51 (s), 33.99 (s), 36.29 (p), 36.48 (p),
36.73 (s), 42.54 (s), 44.36 (2p), 56.49 (s), 104.23 (t), 104.5
(t), 116.04 (2t), 118.22 (t), 118.58 (t), 121.74 (2t), 121.98
(2q), 122.35 (2q), 123.15 (2q), 127.13 (2t), 134.62 (2t),
141.78 (2q), 158.63 (q), 161.67 (q), 167.24 (q), 176.84 (q);
FD-MS: m/z 596 [Mþ], C33H37N7O4.
4.4. General procedure for the preparation of pyrrole
carboxamides with naphthalimide butanoic acid as
building block
Synthesis: see Section 4.3.
4.3.5.
N-2-[3-(Dimethylamino)propyl]-1-methyl-4-{[4-
4.4.1. N-2-[3-(Dimethylamino)propyl]4-{[4-(1,3-dioxo-2,3-
dihydro-1H-benzo[d,e]isochinoline-2-yl)butanoyl]amino}-
1-methyl-1H-2-pyrrole carboxamide (23)
(9-oxo-9,10-dihydro-10-acridinyl)butanoyl] amino}-
1H-2-pyrrole carboxamide (21)
Three hundred and sixty five milligrams of 9, 254 mg 15.
Yellow solid (300 mg) (0.62 mmol) (62%), m.p. 140e
145 ꢀC; IR (KBr, cmꢁ1): 3200, 3000, 2880, 1600, 1570,
1500, 1460, 1440, 1420, 1370, 1350, 1260, 1240, 1160,
1120, 1080, 1020, 910, 730, 660, 590; 1H NMR (DMSO-
d6): d 1.67 (quint., 2H, 3J ¼ 6.9 Hz, CH2), 2.08 (quint.,
2H, CH2), 2.32 (s, 3H, 2CH3), 2.5 (t, 2H, CH2), 2.58 (t,
2H, 3J ¼ 6.2 Hz, CH2), 3.19 (q, 2H, 3J ¼ 6.0 Hz, CH2),
3.79 (s, 3H, pyrrole-CH3), 4.51 (t, 2H, 3J ¼ 8.0 Hz, CH2),
6.71 (s, 1H, pyrrole-H-3), 7.16 (s, 1H, pyrrole-H-5), 7.34
(pt, 2H, 3J ¼ 7.4 Hz, acridone-H), 7.84 (pt, 2H,
3J ¼ 7.3 Hz, acridone-H), 7.97 (pd, 2H, 3J ¼ 8.6 Hz, acri-
done-H-4 þ 5), 8.14 (t, 1H, NH), 8.35 (pd, 2H,
3J ¼ 7.9 Hz, acridone-H-1 þ 8), 9.92 (s, 1H, NH); 13C
NMR (DMSO-d6): d 22.58 (s), 26.67 (s), 32.01 (s), 36.3
(p), 37.02 (s), 44.58 (2p), 45.39 (s), 56.68 (s), 104.12 (t),
116.21 (2t), 117.95 (t), 121.61 (2t), 121.89 (2q), 122.17
(q), 123.29 (q), 127.06 (2t), 134.57 (2t), 141.86 (2q),
161.55 (q), 169.28 (q), 176.81 (q); FD-MS: m/z 488
[Mþ], C28H33N5O3.
Educt: 370 mg 11, 254 mg 15. Yellow solid (170 mg)
(0.35 mmol) (35%), m.p. 125 ꢀC; IR (KBr, cmꢁ1): 3330,
2950, 1650, 1630, 1590, 1520, 1460, 1440, 1340, 1240,
1
1200, 1170, 1160, 1030, 970, 930, 850, 780, 670; H NMR
(DMSO-d6): d 1.63 (quint., 2H, 3J ¼ 6.8 Hz, CH2), 1.94
3
(quint., 2H, J ¼ 7.0 Hz, CH2), 2.21 (s, 6H, 2CH3), 2.31 (2 t,
3
4H, 2CH2), 3.17 (q, 2H, J ¼ 6.0 Hz, CH2), 3.7 (s, 3H, pyr-
3
role-CH3), 4.08 (t, 2H, J ¼ 6.9 Hz, CH2), 6.56 (d, 1H, pyr-
role-H-3), 6.94 (d, 1H, pyrrole-H-5), 7.82 (pt, 2H,
naphthalimide-H-5 þ 8), 8.04 (t, 1H, NH), 8.43 (m, 4H, naph-
thalimide-H-4 þ 6 þ 7 þ 9), 9.73 (s, 1H, NH); 13C NMR
(DMSO-d6): d 24.15 (s), 27.02 (s), 33.66 (s), 36.18 (p),
37.11 (s), one signal below the DMSO-peak, 45.0 (2p),
57.01 (s), 103.48 (t), 117.65 (t), 122.2 (q), 122.4 (2q),
123.12 (q), 127.45 (2t), 127.72 (q), 131.0 (2t), 131.56 (q),
134.52 (2t), 161.44 (q), 163.81 (2q), 169.02 (q); FD-MS: m/
z 490 [Mþ], C27H31N5O4.
4.4.2. N-2-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-
1-methyl-1H-3-pyrrolyl]-4-{[4-(1,3-dioxo-2,3-dihydro-1H-
benzo[d,e]isochinoline-2-yl)butanoyl]amino}-1-methyl-1H-
2-pyrrole carboxamide (24)
4.3.6. N-2-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-
1-methyl-1H-3-pyrrolyl]-1-methyl-4-{[4-(9-oxo-9,10-
dihydro-10-acridinyl)butanoyl]amino}-1H-2-pyrrole-
carboxamide (22)
Educt: 370 mg 11, 376 mg 16. Yellow solid (190 mg)
(0.31 mmol) (31%), m.p. 165 ꢀC; IR (KBr, cmꢁ1): 3300,
2940, 1650, 1590, 1530, 1430, 1400, 1385, 1235, 1140,
Three hundred and sixty five milligrams of 9, 376 mg 16.
Yellow solid (290 mg) (0.48 mmol) (48%), m.p. > 250 ꢀC;
IR (KBr, cmꢁ1): 3360, 3220, 2900, 1610, 1570, 1480, 1440,
1420, 1380, 1360, 1340, 1280, 1250, 1190, 1160, 1080, 920,
800, 750, 660; 1H NMR (DMSO-d6): d 1.67 (quint., 2H,
CH2), 2.09 (quint., 2H, CH2), 2.37 (s, 6H, 2CH3), 2.59 (2 t,
4H, 2CH2), 3.2 (q, 2H, 6.3 Hz, CH2), 3.8 (s, 3H, pyrrole-
CH3), 3.85 (s, 3H, pyrrole-CH3), 4.53 (t, 2H, 3J ¼ 7.7 Hz,
CH2), 6.86 (d, 1H, 4J ¼ 1.7 Hz, pyrrole-H-3), 6.92 (d, 1H,
1
1100, 1045, 780; H NMR (DMSO-d6): d 1.62 (quint., 2H,
3
3J ¼ 7.0 Hz, CH2), 1.95 (quint., 2H, J ¼ 7.0 Hz, CH2), 2.21
(s, 6H, 2CH3), 2.31 (2t, 4H, 2CH2), 3.17 (q, 2H,
3J ¼ 6.0 Hz, CH2), 3.75 (s, 3H, pyrrole-CH3), 3.78 (s, 3H, pyr-
role-CH3), 4.11 (t, 2H, 3J ¼ 6.8 Hz, CH2), 6.78 (s, 1H, pyrrole-
H-3), 6.81 (s, 1H, pyrrole-H-5), 6.99 (s, 1H, pyrrole-H-30),
7.16 (s, 1H, pyrrole-H-50), 7.84 (pt, 2H, 3J ¼ 7.6 Hz, naphtha-
limide-H-5 þ 8), 8.06 (t, 1H, NH), 8.45 (m, 4H, naphthali-
mide-H-4 þ 6 þ 7 þ 9), 9.79 (s, 1H, NH), 9.82 (s, 1H, NH);
13C NMR (DMSO-d6): d 24.17 (s), 27.14 (s), 33.68 (s),
36.24 (p), 36.32 (p), 37.14 (s), one signal below the DMSO-
peak, 45.09 (2p), 57.05 (s), 104.13 (t), 104.35 (t), 118.09 (t),
118.3 (t), 122.27 (q), 122.37 (2q), 122.44 (q), 122.91 (q),
123.22 (q), 127.48 (2t), 127.75 (q), 131.02 (2t), 131.6 (q),
134.53 (2t), 158.64 (q), 161.54 (q), 163.84 (2q), 169.09 (q);
FD-MS: m/z 613 [Mþ], C33H37N7O5.
4
4J ¼ 1.7 Hz, pyrrole-H-5), 7.18 (d, 1H, J ¼ 1.4 Hz, pyrrole-
H-30), 7.21 (d, 1H, pyrrole-H-50), 7.34 (pt, 2H, 3J ¼ 7.4 Hz, ac-
3
ridone-H), 7.84 (pt, 2H, J ¼ 7.0 Hz, acridone-H), 7.99 (pd,
3
3
2H, J ¼ 8.8 Hz, acridone-H-4 þ 5), 8.1 (t, 1H, J ¼ 5.5 Hz,
3
NH), 8.36 (pd, 2H, J ¼ 8.2 Hz, acridone-H-1 þ 8), 9.88 (s,
1H, NH), 9.96 (s, 1H, NH); 13C NMR (DMSO-d6): d 22.59
(s), 26.58 (s), 32.03 (s), 36.28 (p), 36.44 (p), 36.78 (s),
44.41 (2p), 45.4 (s), 56.53 (s), 104.4 (t), 104.5 (t), 116.23