G.A. Pinna et al. / Il Farmaco 58 (2003) 749ꢀ
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759
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4.5.2. N3-{3-[{3-[(1H-Benzo[g] indazole-3-yl-
carbonyl)amino]propyl}(methyl)amino]propyl}-1H-
benzo[g]indazole-3-carboxamide (2b)
285 (4.18), 308 (3.93), 319 (3.81). H NMR (CDCl3):
2.46 (s, 3H), 2.77 (q, 4H, Jꢂ5.6 Hz), 3.62 (q, 4H, Jꢂ
5.6 Hz), 4.13 (s, 6H), 6.70ꢀ6.85 (br s, 2H, NH exch. with
D2O), 7.10ꢀ7.18 (m, 4H), 7.40ꢀ7.60 (m, 6H), 8.25ꢀ8.35
(m, 2H). Anal. Calc. for C31H31N7O2×2C4H4O4×H2O: C
/
/
/
Yield: 27% after purification by trituration with
/
/
/
acetone; white solid; m.p. 230ꢀ
/
232 8C. Rf (CHCl3/
/
/
MeOH 9:1) 0.17. IR (nujol): 1640 (Cꢁ
/
O), 3100ꢀ3160
/
59.46, H 5.76, N 12.45. Found: C 60.07, H 5.74, N
(NH), 3360 (NH). UV (ethanol): lmax 236 (4.34), 248
(4.01), 268 (3.97), 280 (3.80), 291 (3.79), 316 (3.44), 331
12.41%.
1
(3.48). H NMR (CDCl3, DMSO): 1.82ꢀ
/
2.02 (qu., 4H),
3.40 (br s, 4H, NH exch.
3.70 (m, 4H), 7.45ꢀ8.65 (m, 10H and
4.5.6. N3-{3-[{3-[(2-Methyl-2H-benzo[g]indazole-3-
yl-carbonyl)amino]propyl}(methyl) amino]propyl}2-
methyl-2H-benzo[g]indazole-3-carboxamide (2f)
Yield: 30% as an oily residue which solidified on
standing after purification by FC eluting with CHCl3/
CH3OH 9/1; yellowish solid; m.p. 117ꢀ
rated with ethyl ether). Rf (CHCl3/MeOH 9:1) 0.30. IR
(nujol): 1660 (CꢁO), 3300 (NH). UV (ethanol): lmax 239
(4.67), 248 (4.50), 299 (4.32). 319 (4.06), 334 (3.96). H
NMR (CDCl3): 1.70ꢀ1.89 (m, 4H), 2.33 (s, 3H), 2.45ꢀ
2.65 (m, 2H), 3.45ꢀ3.60 (m, 4H), 4.30ꢀ4.15 (br s, 2H,
NH exch. with D2O), 4.30 (s, 6H), 7.25ꢀ8.50 (m, 14H),
2.29 (s, 3H), 2.57 (t, 4H), 3.10ꢀ
/
with D2O), 3.50ꢀ
/
/
2NH exch. with D2O). Anal. Calc. for C31H31N7O2: C
69.77, H 5.86, N 18.37. Found: C 69.84, H 5.63, N
18.56%.
/
118 8C (tritu-
4.5.3. N3-{2-[{2-[(1-Methyl-1H-benzo[g]indazole-3-
yl-carbonyl)amino]ethyl}(methyl)amino]ethyl}-1-
methyl-1H-benzo[g]indazole-3-carboxamide (2c)
Yield: 70% as an oily residue which solidified on
standing after purification by FC eluting with CHCl3/
/
1
/
/
/
/
/
CH3OH 9/1; white solid; m.p. 120ꢀ
with ethyl ether). Rf (CHCl3/MeOH 9:1) 0.50. IR
O), 3100ꢀ3400 (NH). UV (ethanol):
/
122 8C (triturated
10.51 (br s, 2H, NH exch. with D2O). Anal. Calc. for
C33H35N7O2: C 70.57, H 6.28, N 17.46. Found: C 70.46,
H 6.59, N 17.63%.
(nujol): 1650 (Cꢁ
/
/
lmax 221 (4.59), 254 (4.12), 269 (4.00), 280 (4.02), 304
1
(3.65), 320 (3.67). H NMR (CDCl3): 2.48 (s, 3H), 2.75
(t, 4H), 3.65 (q, 4H), 3.98 (s, 6H), 7.11 (br s, 2H, NH
4.5.7. N3-{2-[{2-[(1-Phenyl-1H-benzo[g]indazole-3-yl-
carbonyl)amino]ethyl}(methyl) amino]ethyl}1-phenyl-
1H-benzo[g]indazole-3-carboxamide (2g)
exch. with D2O), 7.25ꢀ8.35 (m, 1H). Anal. Calc. for
/
C31H31N7O2: C 69.77, H 5.86, N 18.37. Found: C 69.83,
H 5.67, N 18.53%.
Yield: 35% as an oily residue after purification by FC
eluting with CHCl3/CH3OH 9/1; yellowish oil; m.p.
118ꢀ
/
120 8C (as hydrochloride). Rf (CHCl3/MeOH 9:1)
4.5.4. N3-{3-[{3-[(1-Methyl-1H-benzo[g] indazole-3-
yl-carbonyl)amino]propyl}(methyl)amino]propyl}1-
methyl-1H-benzo[g]indazole-3-carboxamide[(E)-3-
carboxy-2-propenoate] (2d)
Yield: 53% as an oily residue which solidified on
standing after purification by FC eluting with CHCl3/
0.31. IR (nujol): 1630 (Cꢁ
/
O), 3300ꢀ3400 (NH). UV
/
(ethanol): lmax 220 (4.57), 244 (4.47), 254 (4.41), 279
(4.16), 306 (3.77), 314 (3.57), 320 (3.77). 1H NMR
(CDCl3): 2.40 (s, 3H), 2.73 (t, 4H, Jꢂ
(m, 4H, Jꢂ6.4 Hz), 7.20ꢀ7.50 (m, 16H and 2NH exch.
with D2O), 7.65 (d, 2H, Jꢂ8.8 Hz), 7.88 (d, 2H, Jꢂ8.2
Hz), 8.39 (d, 2H, Jꢂ8.8 Hz). Anal. Calc. for
H2O: C 65.77, H 5.25, Cl 9.47, N
/
6.4 Hz), 3.51ꢀ/3.69
/
/
/
/
CH3OH 8/2; white solid; m.p. 124ꢀ
Rf (CHCl3/MeOH 8:2) 0.47. IR (nujol): 1650 (Cꢁ
3300ꢀ3500 (NH). UV (ethanol): lmax 213 (4.08), 237
(4.33), 260 (3.93), 268 (3.85), 283 (2.87), 295 (3.23), 319
/
125 8C (as fumarate).
/
/O),
C41H35N7O2×
/
2HCl×
/
/
13.10. Found: C 65.87, H 5.09, Cl 9.32, N 12.81%.
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(3.35), 333 (3.57). H NMR (CDCl3): 1.93 (qu 4H, Jꢂ
6.4 Hz), 2.33 (s, 3H), 2.59 (t, 2H, Jꢂ6.4 Hz), 3.64 (q,
4H, Jꢂ6.4 Hz), 4.39 (s, 6H), 6.68 (br s, 2H, NH exch.
with D2O), 7.05ꢀ8.35 (m, 14H). Anal. Calc. for
2C4H4O4: C 61.72, H 5.94, N 12.29.
/
4.5.8. N3-{3-[{3-[(1-Phenyl-1H-benzo[g]indazole-3-yl-
carbonyl)amino]propyl}(methyl) amino]propyl}1-
phenyl-1H-benzo[g]indazole-3-carboxamide (2h)
Yield: 20% as an oily residue after purification by FC
eluting with CHCl3/CH3OH 9/1; yellowish oil; m.p.
/
/
/
C33H35N7O2×
/
Found: C 61.69, H 6.06, N 12.64%.
124ꢀ
/
126 8C (as hydrochloride). Rf (CHCl3/MeOH 9:1)
0.41. IR (nujol): 1660 (Cꢁ
/
O), 3300ꢀ3400 (NH). UV
/
4.5.5. N3-{2-[{2-[(2-Methyl-2H-benzo[g]indazole-3-
yl-carbonyl)amino]ethyl}(methyl)amino]ethyl}2-
methyl-2H-benzo[g]indazole-3-carboxamide[(E)-3-
carboxy-2-propenoate] (2e)
Yield: 42% as an oily residue which solidified on
standing after purification by FC eluting with CHCl3/
(ethanol): lmax 212 (4.48), 223 (4.45), 242 (4.40), 253
(4.37), 273 (4.10), 307 (3.61), 320 (3.63). 1H NMR
(CDCl3): 1.79 (qu, 4H, Jꢂ
4H, Jꢂ6.4 Hz), 3.46ꢀ3.58 (m, 4H, Jꢂ
7.31 (m, 2H), 7.45ꢀ7.64 (m, 16H and 2NH exch. with
D2O), 7.83ꢀ7.95 (m, 2H), 8.42 (d, 2H,, Jꢂ9.0 Hz).
Anal. Calc. for C43H39N7O2×3HCl×3H2O: C 60.81, H
/6.4 Hz), 2.21 (s, 3H), 2.50 (t,
/
/
/
6.4 Hz), 7.21ꢀ
/
/
/
/
CH3OH 9/1; white solid; m.p. 133ꢀ
Rf (CHCl3/MeOH 9:1) 0.51. IR (nujol): 1650 (Cꢁ
3260 (NH). UV (ethanol): lmax 223 (4.55), 242 (4.36),
/
134 8C (as fumarate).
/
/
/O),
5.70, Cl 12.52, N 11.55. Found: C 60.54, H 5.47, Cl
12.35, N 11.25%.