H. D. Lim et al. / Bioorg. Med. Chem. 17 (2009) 3987–3994
3993
8000 scans): d 24.12; 28.86; 31.58; 47.73; 117.29; 123.32; 130.85;
133.18; 133.95; 135.03; 168.83. HRMS (EI) m/z calcd for
C14H17BrN4S: 352.0357; found: 352.0337.
21.74; 131.94; 132.83; 135.69; 136.22; 136.48; 138.24; 171.30.
HRMS (EI) m/z calcd for C15H19BrN4S: 366.0514; found: 366.0500.
6.7.13. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(4-iodo-phenyl)-
ethyl]-isothiourea dihydrobromide (7o)
6.7.7. 2-[3-(Imidazol-4-yl)-propyl]-1-(4-iodo-benzyl)-
isothiourea dihydrobromide (7i)
Isolated yield after crystallization: 18%. Mp: 223–225 °C. 1H
NMR (200 MHz, MeOD): d 1.94–2.02 (m, 2H); 2.80–3.01 (m, 4H);
3.21 (t, J = 7.3 Hz, 2H); 3.65 (t, J = 7.1 Hz, 2H); 7.08 (d, J = 8.3,
2H); 7.39 (s, 1H); 7.65 (d, J = 8.3 Hz, 2H); 8.86 (d, J = 1.3 Hz, 1H).
13C NMR (200 MHz, MeOD, 8000 scans): d 24.09; 28.83; 31.49;
34.27; 46.06; 92.86; 117.28; 132.19 (2C); 133.92; 135.05;
138.75; 138.94 (2C); 168.37. HRMS (EI) m/z calcd for C15H19IN4S:
414.0375; found: 414.083.
Isolated yield after crystallization: 26%. Mp: 201.9–202.9 °C. 1H
NMR (MeOD): d 2.02–2.15 (m, 2H); 2.91 (t, J = 7.60 Hz, 2H); 3.30–
3.40 (m, 2H), 4.57 (s, 2H); 7.15 (d, J = 8.3 Hz, 2H); 7.39 (s, 1H); 7.86
(d, J = 8.3 Hz, 2H); 8.80 (d, J = 1.3 Hz, 1H). 13C NMR (MeOD, 8000
scans): d 24.19; 28.93; 31.62; 47.60; 94.64; 117.29; 130.92 (2C);
134.09; 135.06; 135.62; 139.27 (2C). HRMS (EI) m/z calcd for
C14H17IN4S: 400.0219; found: 400.0208.
6.7.8. 2-[3-(Imidazol-4-yl)-propyl]-1-(4-methyl-benzyl)-
isothiourea dihydrobromide (7j)
6.7.14. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(4-methyl-phenyl)-
ethyl]-isothiourea dihydrobromide (7p)
Isolated yield after crystallization: 15%. Mp: 201.7–203.1 °C. 1H
NMR (MeOD): d 2.02–2.15 (m, 2H); 2.33 (s, 3H); 2.91 (t, J = 7.5 Hz,
2H); 3.20–3.38 (m, 2H), 4.55 (s, 2H); 7.00–7.30 (m, 4H); 7.39 (s,
1H); 8.85 (d, J = 1.4 Hz, 1H). 13C NMR (MeOD, 8000 scans): d
21.17; 24.09; 28.89; 31.57; 47.74; 117.29; 128.96 (2C); 130.66
(2C); 132.68; 133.96; 135.02; 139.54; 168.37. HRMS (EI) m/z calcd
for C15H20N4S: 288.1409; found: 288.1400.
Isolated yield after crystallization: 17%. Mp: 219.0–220.6 °C. 1H
NMR (MeOD): d 1.96–2.02 (m, 2H); 2.27 (s, 3H); 2.79–2.98 (m, 4H);
3.20 (t, J = 7.3 Hz, 2H); 3.64 (t, J = 7.1 Hz, 2H); 7.00–7.21 (m, 4H);
7.37 (s, 1H); 8.82 (s, 1H). 13C NMR (MeOD, 8000 scans): d 21.10;
24.19; 28.85; 31.50; 34.40; 46.56; 117.26; 129.83 (2C); 130.37
(2C); 134.07; 135.05; 135.76; 137.65; 168.20. HRMS (EI) m/z calcd
for C16H22N4S: 302.1565; found: 302.1562.
6.7.9. 2-[3-(Imidazol-4-yl)-propyl]-1-(4-methoxy-benzyl)-
isothiourea dihydrobromide (7k)
6.7.15. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(4-methoxy-phenyl)-
ethyl]-isothiourea dihydrobromide (7q)
Isolate yield after crystallization: 29%. Mp: 196.2–196.5 °C. 1H
NMR (MeOD): d 2.04–2.15 (m, 2H); 2.90 (t, J = 7.6 Hz, 2H); 3.20–
3.33 (m, 2H); 3.79 (s, 3H); 4.51 (s, 2H); 6.94 (d, J = 8.7 Hz, 2H);
7.28 (d, J = 8.6 Hz, 2H); 7.39 (s, 1H); 8.84 (d, J = 1.2 Hz, 1H). 13C
NMR (MeOD, 8000 scans): d 24.86; 29.64; 32.32; 48.50; 56.57;
116.17; 118.03; 128.28; 131.30; 135.80. HRMS (EI) m/z calcd for
C15H20N4OS: 304.1358; found: 304.1350.
Isolated yield after crystallization: 30%. Mp: 172–174 °C. 1H
NMR (MeOD): d 1.93–2.00 (m, 2H); 2.72–2.98 (m, 4H); 3.20 (t,
J = 7.3 Hz, 2H); 3.62 (t, J = 7.1 Hz, 2H); 3.74 (s, 3H); 6.85 (d,
J = 8.6 Hz, 2H); 7.18 (d, J = 8.6 Hz, 2H); 7.37 (s, 1H), 8.84 (s, 1H).
13C NMR (MeOD, 8000 scans): d 24.09; 28.84; 31.49; 33.93;
46.64; 55.71; 115.13 (2C); 117.23; 130.70; 130.95(2C); 135.04.
HRMS (EI) m/z calcd for C16H22N4OS: 318.1514; found: 318.1501.
6.7.10. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(phenyl)-ethyl]-
isothiourea dihydrobromide (7l)
6.7.16. 2-[3-(Imidazol-4-yl)-propyl]-1-(3,3-diphenylpropyl)-
isothiourea dihydrobromide (7r)
Isolated yield after recrystallization from methanol/ethyl ace-
tate (1/1, v/v): 20%. Mp: 178–183 °C. 1H NMR (200 MHz, MeOD):
d 1.91–2.06 (m, 2H); 2.86 (t, J = 7.6 Hz, 2H); 2.97 (t, J = 7.1 Hz,
2H); 3.20 (t, J = 7.3 Hz, 2H); 3.67 (t, J = 7.1 Hz, 2H); 7.09–7.43 (m,
5H); 7.38 (s, 1H); 8.85 (d, J = 1.4 Hz, 1H).
Isolated yield: 27%. The solid decomposes at 85 °C. 1H NMR
(MeOD):
d 1.99–2.13 (m, 2H); 2.39–2.50 (m, 2H), 2.88 (t,
J = 7.5 Hz, 2H); 3.21 (t, J = 7.3 Hz, 2H); 3.23–3.40 (m, 2H), 4.04 (t,
J = 8.0 Hz, 1H); 7.10–7.47 (m, 11H); 8.71 (s, 1H). 13C NMR (MeOD,
8000 scans): d 24.33; 28.92; 31.48; 34.23; 44.32; 117.20; 127.67;
128.81 (5C); 129.76 (5C); 134.36; 135.13; 145.11 (2C); 168.31.
HRMS (EI) m/z calcd for C22H26N4S: 378.1878; found: 378.1880.
13C NMR (200 MHz, MeOD): d 24.04; 28.80; 31.48; 34.78; 46.45;
117.29; 127.98 (2C); 129.79; 129.95(2C); 133.94; 135.04; 138.91;
168.25. HRMS (EI) m/z calcd for C15H20N4S: 288.1409; found:
288.1409.
6.7.17. 2-[3-(Imidazol-4-yl)-propyl]-1-[3-(phenyl)-propyl]-
isothiourea dihydrobromide (7s)
6.7.11. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(4-chloro-phenyl)-
ethyl]-isothiourea dihydrobromide (7m)
Isolated yield after recrystallization from ethanol/diethylether
(1/1, v/v): 20%. Mp: 177–184 °C. 1H NMR (MeOD): d 1.88–2.20
(m, 4H); 2.70 (t, J = 7.7 Hz, 2H); 2.92 (t, J = 7.6 Hz, 2H); 3.14–3.32
(m, 2H); 3.39 (t, J = 7.2 Hz, 2H); 7.11–7.33 (m, 5H); 7.41 (s, 1H);
8.84 (d, J = 1.2 Hz, 1H). 13C NMR (MeOD): d 24.12; 28.87; 30.55;
31.49; 33.78; 45.02; 117.29; 127.29; 129.45(2C); 129.61 (2C);
133.96; 135.02; 142.04; 168.23. HRMS (EI) m/z calcd for
C16H22N4S: 302.1565; found: 302.1568.
Isolated yield after crystallization: 27%. Mp: 205 °C. 1H NMR
(MeOD): d 1.91–2.06 (m, 2H); 2.86 (t, J = 7.7 Hz, 2H); 2.97 (t,
J = 7.1 Hz, 2H); 3.22 (t, J = 7.3 Hz, 2H); 3.66 (t, J = 7.1 Hz, 2H);
7.18–7.32 (m, 4H); 7.39 (s, 1H); 8.85 (d, J = 1.2 Hz, 1H). 13C NMR
(MeOD, 8000 scans): d 24.09; 28.85; 31.49; 34.09; 46.18; 117.27;
129.80 (2C); 131.66 (2C); 133.80; 133.95; 135.04; 137.73;
168.37. HRMS (EI) m/z calcd for C15H19ClN4S: 322.1019; found:
322.1003.
6.7.18. 2-[3-(Imidazol-4-yl)-propyl]-1-[4-phenyl-butyl]-
isothiourea dipicrate (7t)
6.7.12. 2-[3-(Imidazol-4-yl)-propyl]-1-[2-(4-bromo-phenyl)-
ethyl]-isothiourea dihydrosulfate (7n)
Isolated yield after crystallization from ethyl acetate and petro-
leum ether (1/1, v/v): 40%. Mp: 112–134 °C. 1H NMR (MeOD): d
1.60–1.71 (m, 4H); 2.04–2.11 (m, 2H); 2.58–2.72 (m, 2H); 2.89 (t,
J = 7.6 Hz, 2H); 3.22 (t, J = 7.3 Hz, 2H); 3.31–3.41 (m, 2H); 7.09–
7.28 (m, 5H); 7.35 (s, 1H); 8.74 (s, 4H); 8.79 (s, 1H). 13C NMR
(MeOD, 8000 scans): d 24.12; 28.38; 28.83; 29.66; 31.39; 36.25;
45.32; 117.15; 126.65(3C); 126.95(2C); 129.38 (4C); 134.00;
135.02. HRMS (EI) m/z calcd for C17H24N4S: 316.1722; found:
316.1721.
Isolated yield after crystallization from isopropanol: 25%. Mp:
202–203 °C. 1H NMR (MeOD): d 1.92–1.99 (m, 2H); 2.74 (t,
J = 7.37 Hz, 2H); 2.91 (t, J = 7.0 Hz, 2H); 3.13 (t, J = 7.0 Hz, 2H);
3.63 (t, J = 7.4 Hz, 2H); 6.69 (s, 3H); 7.03 (s, 1H); 7.18 (d,
J = 8.4 Hz, 2H); 7.44 (d, J = 8.4 Hz, 2H); 8.07 (s, 1H). 13C NMR
(MeOD, 8000 scans): d 25.38; 29.52; 31.54; 34.22; 46.00; 166.69;