Arch. Pharm. Chem. Life Sci. 2008, 341, 28–41
Pyrido[2,3-d]pyrimidines as Cytotoxics and Pro-Apoptotics
31
Table 2. Spectroscopic data (IR, NMR, and MS) for the new compounds 2, 3, 4, and 6.
Comp.
IR (cm – 1
)
1H-NMR (DMSO-d6, 400 MHz) d ppm, J (Hz)
MS (m/z, % abundance)
2a
2b
2c
3500 – 3200, 1634.
3490 – 3180, 1639.
3500 – 3280, 1628.
1.24 (t, 3H, CH3); 3.13 (q, 2H, CH2); 8.92 (br s, 3H, NH.HI, NH2).
1.23 (d, 6H, 2CH3); 3.89-3.95 (m, 1H, CH); 8.87 (br s, 3H, NH, NH2).
0.92 (t, 3H, CH3); 1.26-1.29 (m, 4H, -S-(CH2)2-(CH2)2-CH3); 1.50-1.60 (m, 2H, -S-CH2-CH2-
(CH2)2-CH3); 3.01-3.16 (m, 2H, -S-CH2-(CH2)3-CH3); 8.88 (br s, 3H, NH.IH, NH2).
0.82 (t, 3H, CH3); 1.19-1.28 (m, 6H, -S-(CH2)2-(CH2)3-CH3); 1.32-1.53 (m, 2H, -S-CH2-CH2-
(CH2)3-CH3); 3.14 (t, 2H, -S-CH2-(CH2)4-CH3); 8.81-8.91 (br s, 3H, NH, NH2).
1.29 (t, 3H, -S-CH2-CH3); 2.97-3.07 (m, 2H, -S-CH2-CH3); 7.55 (dd, 1H, H5); 8.06 (dd, 1H, H4);
8.68 (dd, 1H, H6); 9.65 (br s, 1H, NH); 11.98 (br s, 1H, NH).
1.28 (d, 6H, -S-CH(CH3)2); 3.91-4.01 (m, 1H, -S-CH(CH3)2); 7.44-7.52 (m, 3H, H5, 2NH); 8.46 (dd,
1H, H4); 8.86 (dd, 1H, H6).
0.85 (t, 3H, -S-(CH2)4-CH3); 1.16-1.38 (m, 4H, -S-(CH2)2-(CH2)2-CH3); 1.59-1.66 (m, 2H, -S-CH2-
CH2-(CH2)2-CH3); 3.08 (t, 2H, -S-CH2-(CH2)3-CH3); 7.49 (dd, 1H, H5); 8.16 (dd, 1H, H4); 8.45 (dd,
1H, H6); 9.43 (br s, 2H, 2NH).
2d
3a
3b
3c
3470 – 3290, 1625.
3320 – 3150, 1650.
3300 – 3150, 1650.
3350 – 3150, 1680.
3d
3320 – 3100, 1640.
0.84 (t, 3H, -S-(CH2)5-CH3); 1.27-1.50 (m, 6H, -S-(CH2)2-(CH2)3-CH3); 1.63-1.66 (m, 2H, -S-CH2-CH2-
(CH2)3-CH3); 3.09 (t, 2H, -S-CH2-(CH2)4-CH3); 7.53 (dd, 1H, H5); 8.19 (dd, 1H, H4); 8.47 (dd, 1H, H6);
9.44 (br s, 2H, 2NH).
4a
4b
4c
3100 – 2400, 1685.
3400 – 2430, 1695.
3150 – 2450, 1680.
1.36 (t, 3H, -S-CH2-CH3); 3.26 (q, 2H, -S-CH2-CH3); 5.56 (br s, 1H, NH+); 7.56 (dd, 1H, H6); 8.62 (dd,
1H, H5); 8.91 (dd, 1H, H7).
1.37 (d, 6H, -S-CH(CH3)2); 3.97-4.14 (m, 1H; -S-CH(CH3)2); 7.39 (dd, 1H, H6); 8.37 (dd, 1H, H5);
8.81 (dd, 1H, H7); 12.78 (br s, 1H, NH+).
0.90 (t, 3H, -S-(CH2)4-CH3); 1.36-1.39 (m, 4H, -S-(CH2)2-(CH2)2-CH3); 1.68-1.75 (m, 2H, -S-CH2-
CH2-(CH2)2-CH3); 3.23 (t, 2H, -S-CH2-(CH2)3-CH3); 7.42 (dd, 1H, H6); 8.38 (dd, 1H, H5); 8.85 (dd,
1H, H7); 12.84 (br s, 1H, NH+).
4d
3190 – 2430, 1686.
0.84 (t, 3H, -S-(CH2)5-CH3); 1.28-1.39 (m, 6H, -S-(CH2)2-(CH2)3-CH3); 1.68 (br s, 2H, -S-CH2-CH2-
(CH2)3-CH3); 3.21 (t, 2H, -S-CH2-(CH2)4-CH3); 7.42 (dd, 1H, H6); 8.39 (dd, 1H, H5); 8.90 (dd, 1H,
H7); 13.56 (br s, 1H, NH+).
6a
3490 – 3430, 1625.
3480 – 3430, 1620.
1.24 (t, 3H, -NH-CH2-CH3); 1.36 (t, 3H, -S-CH2-CH3); 3.18 (q, 4H, -NH-CH2-CH3, -S-CH2-CH3); 7.48
(dd, 1H, H6); 8.72-8.75 (m, 2H, H5, NH); 9.15 (dd, 1H, H7).
0.90 (t, 3H, -NH-(CH2)3-CH3); 1.35-1.37 (m, 5H, -S-CH2-CH3, -NH-(CH2)2-CH2-CH3); 1.70-1.72 (m,
2H, -NH-CH2-CH2-CH2-CH3); 3.13 (q, 2H, -S-CH2-CH3); 3.52 (q, 2H, -NH-CH2-(CH2)2-CH3); 7.37
(q, 1H, H6); 8.57-8.61 (m, 2H, H5, NH); 8.83 (dd, 1H, H7).
234 (M+, 89), 219 (21), 205 (37), 201 (62), 173
(67), 159 (67), 103 (100).
262 (M+, 92), 247 (21), 234 (24), 229 (73), 173
(47), 159 (34), 103 (100).
6b
6c
6d
6e
6f
3500 – 3425, 1630.
3480 – 3440, 1630.
3475 – 3430, 1632.
3645 – 3430, 1630.
3600 – 2450, 1632.
0.88 (t, 3H, -NH-(CH2)4-CH3); 1.34-1.36 (m, 7H, -S-CH2-CH3, -NH-CH2-CH2-(CH2)2-CH3); 1.51-1.67
(m, 2H, -NH-CH2-CH2-(CH2)2-CH3); 3.17 (q, 2H, -S-CH2-CH3); 3.53 (t, 2H, -NH-CH2-(CH2)3-CH3);
7.39 (q, 1H, H6); 8.59-8.63 (m, 2H, H5, NH); 8.84 (dd, 1H, H7).
0.86 (t, 3H, -NH-(CH2)5-CH3); 1.35-1.37 (m, 9H, -S-CH2-CH3, -NH-(CH2)2-(CH2)3-CH3); 1.64-1.67
(m, 2H, -NH-CH2-CH2-(CH2)3-CH3); 3.12-3.23 (m, 4H, -NH-CH2-(CH2)4-CH3, -S-CH2-CH3); 7.50 (q,
1H, H6); 8.78-8.87 (m, 2H, H5, NH); 9.39 (br s, 1H, H7).
276 (M+, 82), 261 (16), 247 (17), 243 (68), 229
(15), 201 (10), 173 (98), 159 (19), 103 (100).
290 (M+, 59), 275 (13), 262 (13), 257 (56), 243
(10), 229 (12), 215 (15), 173 (81), 159 (27), 103
(100).
0.85 (t, 3H, -NH-(CH2)6-CH3); 1.30-1.32 (m, 9H, -NH-(CH2)3-(CH2)3-CH3, -S-CH2-CH3); 1.65 (d, 2H,
304 (M+, 59), 289 (13), 276 (15), 271 (47), 229
-NH-(CH2)2-CH2-(CH2)3-CH3); 1.80-1.92 (m, 2H, -NH-CH2-CH2-(CH2)4-CH3); 3.16 (q, 2H, -S-CH2-CH3); (15), 215(8), 173 (88), 159 (29), 103 (100).
3.53 (q, 2H, -NH-CH2-(CH2)5-CH3); 7.39 (q, 1H, H6); 8.58-8.62 (m, 2H, H5, NH); 8.84 (d, 1H, H7).
1.33 (t, 3H, -S-CH2-CH3); 1.78-1.85 (m, 2H, -NH-CH2-CH2-CH2OH); 3.12 (q, 2H, -S-CH2-CH3); 3.53- 264 (M+, 38), 249 (10), 236 (13), 233 (17), 231
3.55 (m, 4H, -NH-CH2-CH2-CH2OH); 4.56 (t, 1H, OH), 7.39 (q, 1H, H6); 8.58-8.61 (m, 2H, H5, NH); (51), 173 (41), 159 (51), 103 (100).
8.84 (d, 1H, H7).
1.36-1.38 (m, 3H, -S-CH2-CH3); 1.51-1.53 (m, 2H, -NH-CH2-CH2-CH2-CH2OH); 1.71-1.73 (m, 2H,
2H, -NH-(CH2)2-CH2-CH2OH); 3.23-3.25 (m, 2H, -S-CH2-CH3); 3.41-3.43 (m, 2H, -NH-CH2-(CH2)2-
CH2OH); 3.64-3.66 (m, 2H, -CH2OH); 4.28 (br s, 1H, OH); 7.67 (br s, 1H, H6); 8.91 (d, 1H, H5);
9.28 (d, 1H, H7); 10.87 (br s, 1H, NH+).
6g
6h
3625 – 2450, 1625.
1.34-1.36 (m, 5H, -NH-(CH2)2-CH2-CH2-CH2OH, -S-CH2-CH3); 1.71-1.73 (m, 4H, -NH-CH2-CH2-CH2-
CH2-CH2OH); 3.21 (q, 2H, -S-CH2-CH3); 3.42 (t, 2H, -NH-CH2-(CH2)3-CH2OH); 3.62-3.64 (m, 2H, -NH-
(CH2)4-CH2OH); 4.02 (br s, 1H, OH); 7.65 (q, 1H, H6); 8.91 (d, 1H, H5); 9.28 (d, 1H, H7); 10.78 (br s,
1H, NH+).
6i
3495 – 3430, 1622.
3485 – 3420, 1633.
3482 – 3435, 1630.
3490 – 3435, 1627.
3480 – 3430, 1630.
3475 – 2435, 1615.
0.98 (t, 3H, -NH-(CH2)3-CH3); 1.39-1.41 (m, 8H, -NH-(CH2)2-CH2-CH3, -S-CH(CH3)2); 1.71-1.73
(m, 2H, -NH-CH2-CH2-CH2-CH3); 3.52-3.54 (m, 2H, -NH-CH2-(CH2)2-CH3); 3.94-4.08 (m, 1H, -
CH(CH3)2); 7.48 (q, 1H, H6); 8.68-8.74 (m, 2H, H5, NH); 8.91 (br s, 1H, H7).
0.89 (t, 3H, -NH-(CH2)4-CH3); 1.37-1.39 (m, 10H, -NH-(CH2)2-(CH2)2-CH3, -S-CH(CH3)2); 1.63-1.65
(m, 2H, -NH-CH2-CH2-(CH2)2-CH3); 3.51 (q, 2H, -NH-CH2-(CH2)3-CH3); 3.90-4.04 (m, 1H, -S-
CH(CH3)2); 7.46 (q, 1H, H6); 8.73 (d, 1H, H5); 8.86 (d, 1H, H7); 9.13 (br s, 1H, NH).
276 (M+, 44), 261 (33), 243 (100), 234 (48),
220 (15), 201 (42), 192 (88), 173 (46), 159 (38),
103 (99).
290 (M+, 27), 275 (22), 257 (81), 248 (25), 234
(19), 220 (22), 205 (68), 192 (38), 173 (100),
159 (17), 103 (65).
6j
6k
6l
0.88 (t, 3H, -NH-(CH2)5-CH3); 1.31 (d, 6H, -S-CH(CH3)2); 1.36-1.38 (m, 6H, -NH-(CH2)2-(CH2)3-CH3); 304 (M+, 34), 289 (25), 271 (100), 262 (27),
1.65-1.67 (m, 2H, -NH-CH2-CH2-(CH2)3-CH3); 3.52 (q, 2H, -NH-CH2-(CH2)4-CH3); 3.93-4.00 (m, 1H, 248 (17), 234 (15), 205 (68), 192 (51), 173 (99),
-S-CH(CH3)2); 7.45 (q, 1H, H6); 8.71 (d, 1H, H5); 8.85 (d, 1H, H7); 8.98 (br s, 1H, NH).
0.86 (t, 3H, -NH-(CH2)6-CH3); 1.27-1.29 (m, 8H, -NH-(CH2)2-(CH2)4-CH3); 1.35 (d, 6H, -S-(CH3)2);
1.64-1.66 (m, 2H, -NH-CH2-CH2-(CH2)4-CH3); 3.52 (t, 2H, -NH-CH2-(CH2)5-CH3); 3.95-3.97 (m, 1H
-S-CH(CH3)2); 7.44 (q, 1H, H6); 8.69 (d, 1H, H5); 8.85 (d, 1H, H7); 9.05 (br s, 1H, NH).
1.38 (d, 6H, -S-CH-(CH3)2); 1.76-1.78 (m, 2H, -NH-CH2-CH2-CH2OH); 3.54-3.56 (m, 4H, -NH-CH2-
CH2-CH2OH); 3.90-3.97 (m, 1H, -S-CH-(CH3)2); 4.55 (t, 1H, OH), 7.39 (q, 1H, H6); 8.57-8.61 (m,
2H, H5, NH); 8.83 (d, 1H, H7).
0.88-0.90 (m, 6H, -NH-(CH2)3-CH3, -S-(CH2)4-CH3); 1.40-1.42 (m, 6H, -NH-(CH2)2-CH2-CH3, -S-(CH2)2-
(CH2)2-CH3); 1.71-1.73 (m, 4H, -NH-CH2-CH2-CH2-CH3, -S-CH2-CH2-(CH2)2-CH3); 3.18 (t, 2H, -S-CH2-
(CH2)3-CH3); 3.43 (q, 2H, -NH-CH2-(CH2)2-CH3); 7.39 (q, 1H, H6); 7.89 (br s, 1H, H+); 8.74 (d, 1H,
H5), 8.92 (d, 1H, H7).
159 (17), 103 (95).
318 (M+, 29), 303 (22), 285 (100), 205 (64),
192 (59), 173 (98), 160 (82), 159 (18), 103 (89).
6m
6n
M+ not observed, 248 (86), 215 (67), 205 (35),
192 (8), 173 (38), 159 (61), 103 (100).
6o
3490 – 2400, 1618.
0.89-0.91 (m, 6H, -NH-(CH2)4-CH3, -S-(CH2)4-CH3); 1.34-1.36 (m, 8H, -NH-(CH2)2-(CH2)2-CH3, -S-
(CH2)2-(CH2)2-CH3); 1.70-1.72 (m, 4H, -NH-CH2-CH2-(CH2)2-CH3, -S-CH2-CH2-(CH2)2-CH3); 3.14 (t,
2H, -S-CH2-(CH2)3-CH3); 3.44 (t, 2H, -NH-CH2-(CH2)3-CH3); 7.54 (q, 1H, H6); 8.42 (dd, 1H, H5);
8.78 (dd, 1H, H7); 9.45 (br s, 1H, NH+).
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