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J = 7.85 Hz, H-30 and H-50), 6.97 (d, 1H, J = 16.55 Hz,
@CH styryl), 6.89 (t, 1H, J = 7.85 Hz, H-40), 6.87 (d,
2H, J = 7.85 Hz, H-20 and H-60), 5.34 (sl, 1H, , OH),
4.36 (m, 1H, CH), 4.22 (m, 2H, NCH2), 3.98 (m, 2H,
127.9 (C-200 and C-600), 120.5 (C-40), 114.8 (C-300 and
C-500), 114.5 (C-100), 114.4 (C-20 and C-60), 107.8 (C-5),
70.3 (OCH2), 65.9 (CH), 64.6 (OCH2-Ar), 45.4
(NCH2). Anal. Calcd for C22H20N4O7: C, 58.40; H,
4.45; N, 12.38. Found: C, 58.22; H, 4.53; N, 12.49.
13
OCH2). C NMR (DMSO-d6) d: 158.5 (C-10), 154.4
(C-6), 151.2 (C-2), 150.3 (C-8), 149.1 (C-4), 135.4
(C@C styryl), 134.8 (C@C styryl), 129.4 (C-30 and C-
50), 129.1 (C-100), 129.0 (C-300 and C-500), 127.1 (C-200
and C-600), 120.5 (C-40), 115.8 (C-400), 114.4 (C-20 and
C-60), 107.7 (C-5), 70.4 (OCH2), 65.8 (CH), 45.5
(NCH2). Anal. Calcd for C22H20N4O4: C, 65.34; H,
4.98; N, 13.85. Found: C, 65.45; H, 4.86; N, 13.98.
5.1.7.11.
3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-(4-
cinnamyl)xanthine (1k). Orange crystals (65%);
mp > 400 ꢁC. IR (KBr) m: 3420-2805 (OH), 1700, 1685
and 1665 (CO). H NMR (DMSO-d6) d: 13.85 (sl, 1H,
1
N7-H), 12.42 (sl, 1H, CO2H), 11.15 (s, 1H, N1-H), 8.05
(d, 2H, J = 7.30 Hz, H-200 and H-600), 7.78 (d, 2H,
J = 7.30 Hz, H-300 and H-500), 7.61 (d, 1H, J = 16.10 Hz,
@CH styryl), 7.24 (m, 2H, H-30, H-50), 6.87 (m, 3H, H-
20, H-40 and H-60), 6.61 (d, 1H, J = 16.10 Hz, @CH sty-
ryl), 5.33 (m, 1H, OH), 4.39 (m, 1H, CH), 4.23 (m, 2H,
NCH2), 4.00 (m, 2H, OCH2). 13C NMR (DMSO-d6) d:
167.5 (CO2H), 158.5 (C-10), 154.6 (C-6), 151.2 (C-2),
150.2 (C-8), 148.6 (C-4), 143.0 (C@C styryl), 135.7
(C@C styryl), 130.0 (C-100), 129.4 (C-30 and C-50), 128.7
(C-200 and C-600), 126.6 (C-300 and C-500), 120.4 (C-40),
114.4 (C-20 and C-60), 108.6 (C-5), 70.3 (OCH2), 65.9
(CH), 45.5 (NCH2). Anal. Calcd for C23H20N4O6: C,
61.60; H, 4.49; N, 12.49. Found: C, 61.86; H, 4.32; N,
12.60.
5.1.7.7. 3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-(3-chloro-
styryl)xanthine (1g). Beige crystals (60%); mp 274 ꢁC. IR
(KBr) m: 3430 (OH), 3150 and 3025 (NH), 1690 and 1665
(CO). 1H NMR (DMSO-d6) d: 13.54 (sl, 1H, N7-H),
11.13 (s, 1H, N1-H), 7.66 (m, 1H, H-200), 7.55–7.39 (m,
4H, H-400, H-500, H-600 and @CH), 7.24 (t, 2H,
J = 7.30 Hz, H-30 and H-50), 7.04 (d, 1H, J = 16.65 Hz,
@CH styryl), 6.87 (m, 3H, H-20, H-40 and H-60), 5.36 (sl,
1H, OH), 4.36 (m, 1H, CH), 4.14 (m, 2H, NCH2), 3.97
(m, 2H, OCH2). Anal. Calcd for C22H19ClN4O4: C,
61.73;H,4.96;N,12.00. Found:C, 60.88;H,5.02;N,12.11.
5.1.7.8.
3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-(3-
methoxystyryl)xanthine (1h). Beige crystals (84%); mp
286 ꢁC. IR (KBr) m: 3450 (OH), 3150 and 3025 (NH),
1680 and 1655 (CO). 1H NMR (DMSO-d6) d: 13.46
(sl, 1H, N7-H), 11.07 (s, 1H, N1-H), 7.54 (d, 1H,
J = 16.90 Hz, @CH), 7.33–7.15 (m, 5H, H-400, H-500, H-
600, H-30 and H-50), 7.00 (d, 1H, J = 16.90 Hz, @CH),
6.88 (m, 4H, H-200, H-20, H-40 and H-60), 5.32 (sl, 1H,
OH), 4.37 (m, 1H, CH), 4.18 (m, 1H, NCH2), 4.11 (m,
1H, NCH2), 3.98 (m, 2H, OCH2), 3.81 (s, 3H, OCH3).
Anal. Calcd for C23H22N4O5: C, 63.58; H, 5.10; N,
12.90. Found: C, 63.71; H, 5.02; N, 13.05.
5.1.7.12. 3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-cyclo-
pentylxanthine (1l). Beige crystals (55%); mp 213 ꢁC.
IR (KBr) m: 3430 (OH), 3150 and 3025 (NH), 1690
1
and 1665 (CO). H NMR (DMSO-d6) d: 13.00 (sl, 1H,
N7-H), 10.96 (s, 1H, N1-H), 7.22 (t, 2H, J = 7.45 Hz,
H-30 and H-50), 6.88 (t, 1H, J = 7.45 Hz, H-40), 6.78
(d, 2H, J = 7.45 Hz, H-20 and H-60), 5.33 (sl, 1H, OH),
4.27 (m, 1H, CH), 4.04 (m, 2H, NCH2), 3.92 (m, 2H,
OCH2), 3.04 (m, 1H, CH cycl.), 1.90 (m, 2H, CH2 cycl.),
1.66 (m, 6H, CH2 cycl.). 13C NMR (DMSO-d6) d: 158.4
(C-8), 157.5 (C-10), 154.4 (C-6), 151.2 (C-2), 149.6 (C-4),
129.3 (C-30 and C-50), 120.5 (C-40), 114.2 (C-20 and C-
60), 106.5 (C-5), 70.4 (OCH2), 65.8 (OCH), 45.4
(NCH2), 38.7 (CH cycl.), 31.8 (CH2 cycl.), 25.0 (CH2
cycl.). Anal. Calcd for C19H22N4O4: C, 61.61; H, 5.99;
N, 15.13. Found: C, 61.53; H, 6.08; N, 15.25.
5.1.7.9. 3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-(3,4,5-
trimethoxystyryl)xanthine (1i). Pale-yellow crystals
(76%); mp 189 ꢁC. IR (KBr) m: 3415 (OH), 3140 and
1
3030 (NH), 1690 and 1670 (CO). H NMR (DMSO-
d6) d: 13.44 (sl, 1H, N7-H), 11.10 (s, 1H, N1-H), 7.52
(d, 1H, J = 16.15 Hz, @CH), 7.25 (m, 2H, H-30 and H-
50), 7.03 (d, 1H, J = 16.15 Hz, @CH), 6.90 (m, 5H, H-
20, H-40, H-60, H-200 and H-600), 5.34 (sl, 1H, OH), 4.36
(m, 1H, CH), 4.06 (m, 2H, NCH2), 3.96 (m, 2H,
OCH2), 3.83 (s, 6H, 2 CH3O–), 3.68 (s, 3H, CH3O–).
Anal. Calcd for C25H26N4O7: C, 60.72; H, 5.30; N,
11.33. Found: C, 60.86; H, 5.23; N, 11.06.
5.1.7.13. 3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-cyclo-
hexylxanthine (1m). Beige crystals (75%); mp 115 ꢁC.
IR (KBr) m: 3430 (OH), 3150 and 3025 (NH), 1690
1
and 1665 (CO). H NMR (DMSO-d6) d: 12.95 (sl, 1H,
N7-H), 10.98 (s, 1H, N1-H), 7.21 (t, 2H, J = 7.0 Hz, H-
30 and H-50), 6.89 (t, 1H, J = 7.0 Hz, H-40), 6.86 (d,
2H, J = 7.0 Hz, H-20 and H-60), 5.33 (sl, 1H, OH),
4.27 (m, 1H, CH), 4.05 (m, 2H, NCH2), 3.92 (m, 2H,
OCH2), 2.62 (m, 1H, CH cycl.), 1.72 (m, 5H, CH2 cycl.),
1.42 (m, 5H, CH2 cycl.). 13C NMR (DMSO-d6) d: 158.4
(C-8), 157.8 (C-10), 154.5 (C-6), 151.2 (C-2), 149.5 (C-4),
129.4 (C-30 and C-50), 120.5 (C-40), 114.3 (C-20 and C-
60), 106.4 (C-5), 70.4 (OCH2), 65.9 (OCH), 45.4
(NCH2), 37.5 (CH cycl.), 30.9 (CH2 cycl.), 30.8 (CH2
cycl.). Anal. Calcd for C20H24N4O4: C, 62.48; H, 6.29;
N, 14.57. Found: C, 62.59; H, 6.20; N, 14.46.
5.1.7.10.
3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-(4-
carboxymethyloxyphenyl)xanthine (1j). Beige crystals
(60%); mp 243 ꢁC. IR (KBr) m: 3500–2830 (OH), 1715,
1690 and 1655 (CO). 1H NMR (DMSO-d6) d: 13.52
(sl, 1H, N7-H), 12.10 (sl, 1H, CO2H), 11.07 (s, 1H,
N1-H), 7.96 (d, 2H, J = 8.10 Hz, H-200 and H-600), 7.24
(m, 2H, H-30 and H-50), 6.94 (m, 5H, H-300, H-500, H-
20, H-40 and H-60), 5.32 (m, 1H, OH), 4.74 (s, 2H,
CH2O), 4.38 (m, 1H, CH), 4.13 (m, 2H, NCH2), 3.99
(m, 2H, OCH2). 13C NMR (DMSO-d6) d: 170.0
(CO2H), 159.3 (C-400), 158.5 (C-10), 154.5 (C-6), 151.2
(C-2), 150.2 (C-8), 149.7 (C-4), 129.4 (C-30 and C-50),
5.1.7.14.
3-[1-(2-Hydroxy-3-phenoxypropyl)]-8-nor-
adamantylxanthine (1n). Beige crystals (75%); mp
135 ꢁC. IR (KBr) m: 3440 (OH), 3150 and 3030 (NH),