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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1223, 1038. 1H-NMR (300 MHz, CDCl3/(D6)DMSO): 3.40 (s, MeN); 3.63 (s, MeN); 3.95 (s, MeO); 4.34
(t, J¼4.92, CH2N); 4.48 (t, J ¼ 4.77, CH2O); 6.91 (d, Jo ¼9.10, 1 arom. H); 7.10 (s, 1 imidazole H); 7.26 (s,
1 imidazole H); 7.73 (dd, Jo ¼8.44, Jm ¼1.76, 1 arom. H); 7.77 (d, Jm ¼1.6, 1 arom. H); 7.99 (s, 1 imidazole
H). Anal. calc. for C19H20N6O4 (396): C 57.57, H 5.09, N 21.20; found: C 57.74, H 4.84, N 21.09.
3,7-Dihydro-8-{3-[3-(1H-imidazol-1-yl)propoxy]-4-methoxyphenyl}-1,3-dimethyl-1H-purine-2,6-di-
one (5c). Yield: 0.3 g (69.23%). M.p. 2368. IR (KBr): 3320, 1680, 1620, 1480, 1200. 1H-NMR (300 MHz,
CDCl3/(D6)DMSO): 2.29 (quint., J¼6.15, CH2); 3.42 (s, MeN); 3.63 (s, MeN); 3.93 (s, MeO); 4.02 (t, J ¼
5.70, CH2); 4.25 (t, J¼6.65, CH2O); 6.97–7.03 (m, 2 imidazole H, 1 arom. H); 7.37 (s, 1 arom. H), 7.60 (s,
1 imidazole H); 12.85 (s, NH). Anal. calc. for C20H22N6O4 (410.43): C 58.52, H 5.40, N 20.48; found: C
58.48, H 5.12, N 19.98.
3,7-Dihydro-8-{3-[3-(1H-imidazol-1-yl)propoxy]phenyl}-1,3-dimethyl-1H-purine-2,6-dione (5d).
Yield: 0.16 g (36.69%). M.p. 218–2208. FT-IR (KBr): 3190, 2950, 1700, 1650, 1450, 1210. 1H-NMR
(300 MHz, CDCl3/(D6)DMSO): 2.26 (quint., J¼6.10, CH2CH2CH2); 3.32 (s, MeN); 3.56 (s, MeN); 4.00
(t, J¼5.65, CH2N); 4.22 (t, J¼6.70, CH2O); 6.85 (s, 2 imidazole H); 7.04 (s, 1 arom. H); 7.32 (t, Jo ¼7.90, 1
arom. H); 7.54 (s, 1 imidazole H); 7.70–7.74 (m, 2 arom. H). Anal. calc. for C19H20N6O3 (380.4): C 59.99,
H 5.30, N 22.09; found: C 59.94, H 5.30, N 21.87.
3,7-Dihydro-8-{4-[3-(1H-imidazol-1-yl)propoxy]-3-methoxyphenyl}-1,3-dimethyl-7-propyl-1H-pu-
rine-2,6-dione (7). Yield: 0.18 g (40.74%). M.p. 158–1608. FT-IR (KBr): 2963, 1690, 1655, 1537, 1477,
1418, 1227, 1033. 1H-NMR (300 MHz, CDCl3): 0.89 (t, J¼7.39, MeCH2); 1.84–1.91 (m, MeCH2); 2.29–
2.37 (m, CH2CH2CH2); 3.44 (s, MeN); 3.63 (s, MeN); 3.95 (s, MeO); 4.01 (t, J ¼ 5.77, CH2O); 4.26–4.33
(m, 2 CH2N); 6.92 (d, Jo ¼8.28, 1 arom. H); 7.00 (s, 1 imidazole H); 7.11–7.14 (m, 2 arom. H), 7.18 (s, 1
imidazole H); 7.75 (s, 1 imidazole H). Anal. calc. for C23H28N6O4 (452.5): C 61.05, H 6.24, N 18.57; found:
C 60.72, H 6.18, N 18.41.
3,7-Dihydro-8-{4-[3-(1H-imidazol-1-yl)propoxy]-3-methoxyphenyl}-1,3,7-trimethyl-1H-purine-2,6-
dione (9). Yield: 0.32 g (74.07%). M.p. 180–1848. FT-IR (KBr): 2959, 1694, 1649, 1538, 1488, 1426, 1259,
1034. 1H-NMR (300 MHz, CDCl3): 2.27–2.35 (m, CH2CH2CH2); 3.43 (s, MeN); 3.62 (s, MeN); 3.96 (s,
MeN); 4.00 (t, J¼5.74, CH2N); 4.05 (s, MeO); 4.26 (t, J¼5.84, CH2O); 6.91 (d, Jo ¼8.48, 1 arom. H);
6.99–7.02 (m, 1 arom. H); 7.09 (s, 1 imidazole H); 7.17 (dd, Jo ¼8.34, Jm ¼1.73, 1 arom. H); 7.22 (m, 1
imidazole H); 7.24 (s, 1 imidazole H). Anal. calc. for C21H24N6O4 (424.45): C 59.42, H 5.70, N 19.80;
found: C 59.12, H 5.41, N 19.47.
3,7-Dihydro-8-{3-[3-(1H-imidazol-1-yl)propoxy]phenyl}-1,3-dimethyl-7-propyl-1H-purine-2,6-dione
(11). Yield: 0.18 g (50.92%). M.p. 128–1308. FT-IR (KBr): 3114, 2954, 1694, 1652, 1539, 1459, 1223, 1045.
1H-NMR (300 MHz, CDCl3): 0.86 (t, J¼7.67, MeCH2); 1.79–1.86 (m, MeCH2); 2.25–2.33 (m,
CH2CH2CH2); 3.44 (s, MeN); 3.62 (s, MeN); 3.99 (t, J¼5.71, CH2O); 4.19–4.34 (m, 2 CH2N); 6.95 (s,
1 imidazole H); 7.02 (dd, Jo ¼8.23, Jm ¼2.63, 1 arom. H); 7.11 (s, 1 imidazole H); 7.16–7.20 (m, 2 arom.
H); 7.43 (t, Jo ¼7.98, 1 arom. H); 7.75 (s, 1 imidazole H). Anal. calc. for C22H26N6O3 (422.48): C 62.54, H
6.20, N 19.89; found: C 62.28, H 5.95, N 19.47.
3,7-Dihydro-8-{4-[3-(1H-imidazol-1-yl)propoxy]-3-methoxyphenyl}-3-methyl-1H-purine-2,6-dione
(14a). Yield: 0.32 g (73.66%). M.p. >3008. FT-IR (KBr): 3155, 3039, 2941, 1688, 1592, 1498, 1423, 1391,
1249, 1029. 1H-NMR (300 MHz, CDCl3/(D6)DMSO): 2.44–2.48 (m, CH2CH2CH2); 3.70 (s, MeN); 3.94
(s, MeO); 4.17 (t, J¼5.33, CH2N); 4.52 (t, J¼6.37, CH2O); 7.01 (d, Jo ¼8.58, 1 arom. H); 7.42 (s, 1 arom.
H, 1 imidazole H); 7.58 (s, 1 imidazole H); 7.67 (dd, Jo ¼8.61, Jm ¼1.67, 1 arom. H); 8.74 (s, 1 imidazole
H). Anal. calc. for C19H20N6O4 (396.4): C 57.57, H 5.08, N 21.20; found: C 57.85, H 4.78, N 20.98.
3,7-Dihydro-8-{4-[3-(1H-imidazol-1-yl)propoxy]-3-methoxyphenyl}-3-methyl-1-propyl-1H-purine-
2,6-dione (14b). Yield: 0.33 g (77.39%). M.p. 226–2308. FT-IR (KBr): 3120, 2959, 1694, 1652, 1567, 1488,
1319, 1265, 1076. 1H-NMR (300 MHz, CDCl3): 0.97 (t, J¼8.88, MeCH2); 1.67–1.74 (m, MeCH2); 2.30–
2.34 (m, ClCH2CH2); 3.68 (s, MeN); 3.98 (s, MeO); 4.03 (t, J ¼ 7.23, 2 CH2N); 4.28 (t, J¼6.31, CH2O);
6.87 (d, Jo ¼7.88, 1 arom. H); 6.97 (s, 1 imidazole H); 7.12 (s, 1 imidazole H); 7.68–7.76 (m, 3 arom. H, 1
imidazole H). Anal. calc. for C22H26N6O4 (438.48): C 60.26, H 5.98, N 19.17; found: C 60.14, H 5.73, N
18.88.
Biological Activity. Radioligand-binding assays of xanthine analogs were performed using cloned
human adenosine A1 and A2A receptors and [3H]DPCPX and [3H]ZM 241385 as radioligands, resp.
[3H]DPCPX from Tocris Cookson (Bristol, UK) with specific activity 3.8 TBq/mmol, concentration