F.-Z. Liu et al. / Bioorg. Med. Chem. 16 (2008) 578–585
583
2
(
1
(
1
8
.08 (t, J = 7.43 Hz, 2H), 2.72–2.77 (m, 1H), 3.08–3.16
m, 3H), 3.56 (m, 1H) 4.32–4.38 (m, 1H), 4.45 (br s,
H), 7.12–7.16 (m, 1H), 7.38–7.42 (m, 1H), 7.76–7.78
m, 1H), 7.85–7.87 (d, J = 6.76 Hz, 1H), 7.93 (br s,
J = 1.33, 7.72 Hz, 1H), 7.54–7.55 (dd, J = 1.35,
8.03 Hz, 1H), 7.65–7.66 (d, J = 7.48 Hz, 1H), 7.92 (br
s, 2H), 8.17–8.18 (d, J = 6.18 Hz, 1H), 8.53 (br s, 1H),
8.91 (br s, 1H), 9.89 (br s, 1H), 10.36 (s, 1H). ESI-MS:
+
H), 8.21–8.23 (d, J = 6.18 Hz, 1H), 8.53 (br s, 1H),
.91 (br s, 1H), 10.09 (br s, 1H), 10.57 (s, 1H). ESI-
m/z [M+H] 440.7.
+
MS: m/z [M+H] 442.4.
5.2.18. (2S,4S)-N-(3-Chlorophenyl)-4-(6-(3-nitroguanidi-
no)hexanamido)pyrrolidine-2-carboxamide hydrochloride
(25). White solid, yield: 65%. Mp: 108–110 °C; IR (KBr,
5.2.14. (2S,4S)-N-(3,4-Difluorophenyl)-4-(6-(3-nitrogua-
nidino)hexanamido)pyrrolidine-2-carboxamide hydrochlo-
ꢀ
1
cm ) v
3240, v
3059, v 2934, v 2858, v
Ar–H CH CH C@O
NH
ride (21). White solid, yield: 79%. Mp: 159–160 °C; IR
1692, 1634, v
1596, vNH 1544, vCH 1430, vN–NO2
Ar,C–C
ꢀ
1
KBr, cm ) v
1
(
3295, v
3065, v
2942, v
1280. H NMR (DMSO-d ) d 1.20–1.25 (m, 2H), 1.45–
NH
Ar–H
CH
C@O
6
1
1
1
693, 1634, v
1541, vAr,C–C 1517, vCH 1423, vN–NO2
1.50 (m, 4H), 1.87–1.92 (m, 1H), 2.04–2.08 (t,
J = 7.42 Hz, 2H), 2.73–2.78 (m, 1H), 3.11 (m, 3H),
3.46–3.49 (m, 1H), 4.34–4.35 (m, 1H), 4.42–4.46 (t,
J = 6.39 Hz, 1H), 7.17–7.20 (d, J = 5.91 Hz, 1H), 7.37–
7.41 (t, J = 6.06 Hz, 1H), 7.53–7.55 (d, J = 6.81 Hz,
1H), 7.82–7.83 (t, J = 1.96 Hz, 1H), 7.92 (br s, 2H),
8.18–8.20 (d, J = 4.71 Hz, 1H), 8.5 (br s, 1H), 8.90 (br
s, 1H), 10.06 (br s, 1H), 11.17 (s, 1H). ESI-MS: m/z
NH
1
266. H NMR (DMSO-d ) d 1.20–1.25 (m, 2H), 1.45–
.50 (m, 4H), 1.83–1.88 (m, 1H), 2.04–2.08 (t,
6
J = 7.40 Hz, 2H), 2.69–2.73 (m, 1H), 3.03–3.06 (m,
1
2
H), 3.11 (br s, 2H), 3.43–3.46 (m, 1H), 4.31–4.38 (m,
H), 7.39–7.41 (m, 1H), 7.43–7.48 (m, 1H), 7.79–7.83
(
1
m, 1H), 7.93 (br s, 2H), 8.15–8.16 (d, J = 6.36 Hz,
H), 8.51 (br s, 1H), 8.99 (br s, 1H), 11.11 (s, 1H).
ESI-MS: m/z [M+H] 442.8.
+
+
[M+H] 440.7.
5.2.15. (2S,4S)-N-(3,5-Difluorophenyl)-4-(6-(3-nitrogua-
nidino)hexanamido)pyrrolidine-2-carboxamide hydrochlo-
5.2.19. (2S,4S)-N-(4-Chlorophenyl)-4-(6-(3-nitroguanidi-
no)hexanamido)pyrrolidine-2-carboxamide hydrochloride
ride (22). White solid, yield: 75%. Mp: 140–142 °C; IR
(26). White solid, yield: 63%. Mp: 116–118 °C; IR (KBr,
ꢀ
1
ꢀ1
(
KBr, cm ) v
858, v
3294, v
1697, 1623, v
3088, v
2940, v
1565, vCH 1479, 1440,
cm ) v
1692, 1631, v
3242, v
3056, v 2939, v 2858, v
Ar–H CH CH C@O
NH
Ar–H
CH
CH
NH
2
1492, vNH 1547, vCH 1397, vN–NO2
1287. H NMR (DMSO-d ) d 1.21–1.25 (m, 2H), 1.45–
C@O
NH
Ar,C–C
1
1
v
N–NO2 1265. H NMR (DMSO-d ) d 1.25–1.26 (m,
6
6
2
(
3
H), 1.47–1.51 (m, 4H), 1.88–1.93 (m, 1H), 2.06–2.09
t, J = 5.34 Hz, 2H), 2.79–2.86 (m, 1H), 3.14 (br s,
H), 3.49–3.57 (br s, 1H), 4.34–4.39 ( m, 1H), 4.50 (br
1.52 (m, 4H), 1.85–1.88 (m, 1H), 2.05–2.08 (t,
J = 7.40 Hz, 2H), 2.75–2.82 (m, 1H), 3.12–3.17 (br s,
3H), 3.47–3.48 (m, 1H), 4.32–4.36 (m, 1H), 4.42–4.45
(t, J = 4.40 Hz, 1H), 7.41–7.43 (d, J = 8.83 Hz, 2H),
7.69–7.71 (d, J = 8.87 Hz, 2H), 7.95 (br s, 2H), 8.20–
8.21 (d, J = 6.02 Hz, 1H), 8.52 (br s, 1H), 8.89 (br s,
1H), 10.08 (br s, 1H), 11.13 (s, 1H). ESI-MS: m/z
s, 1H), 6.96–7.00 (t, J = 6.84 Hz, 1H), 7.43–7.45 (d,
J = 5.94 Hz, 2H), 7.96 (br s, 2H), 8.25–8.26 (d,
J = 4.26 Hz, 1H), 8.51 (br s, 1H), 8.97 (br s, 1H),
+
1
4
0.21 (br s, 1H), 11.68 (s, 1H). ESI-MS: m/z [MꢀH]
+
40.8.
[M+H] 440.7.
5
.2.16. (2S,4S)-4-(6-(3-Nitroguanidino)hexanamido)-N-
5.2.20. (2S,4S)-N-(2,4-Dichlorophenyl)-4-(6-(3-nitrogua-
nidino)hexanamido)pyrrolidine-2-carboxamide hydrochlo-
(2,3,4-trifluorophenyl)pyrrolidine-2-carboxamide hydro-
chloride (23). White solid, yield: 65%. Mp: 132–
ride (27). White solid, yield: 73%. Mp: 147–149 °C; IR
ꢀ
1
ꢀ1
1
1
1
1
34 °C; IR (KBr, cm ) vNH 3296, vCH 2941, v
v
(KBr, cm ) v
1635, v
3226-3382, v
1589, vNH 1532, vCH 1383, vN–NO2 1287.
2937, v
1696,
C@O
CH C@O
NH
CH
694, 1639, v
1543, vAr,C–C 1513, vCH 1482, vN–NO2
NH
Ar,C–C
1
1
266. H NMR (DMSO-d ) d 1.20–1.26 (m, 2H),
H NMR (DMSO-d ) d 1.23–1.26 (m, 2H), 1.46–1.51
6
6
.45–1.50 (m, 4H), 1.88–1.91 (m, 1H), 2.04–2.08 (t,
(m, 4H), 1.90–1.93 (m, 1H), 2.05–2.08 (t, J = 7.42 Hz,
2H), 2.75–2.78 (m, 1H), 3.06–3.31 (m, 3H), 3.47–3.48
(m, 1H), 4.35–4.38 (m, 1H), 4.51–4.54 (m, 1H), 7.49–
7.50 (dd, J = 2.36, 8.67 Hz, 1H), 7.66–7.68 (d,
J = 8.68 Hz, 1H) 7.74–7.75 (d, J = 2.35 Hz, 1H), 7.89
(br s, 2H), 8.19–8.20 (d, J = 6.35 Hz, 1H), 8.51 (br s,
1H), 8.92 (br s, 1H), 10.0 (br s, 1H), 10.45 (s, 1H).
J = 7.41 Hz, 2H), 2.67–2.71 (m, 1H), 2.98–3.01 (t,
J = 7.41 Hz, 1H), 3.14 (br s, 2H), 3.47–3.48 (m, 1H),
4.15–4.16 (br s, 1H), 4.29–4.32 (m, 1H), 4.39–4.41 (t,
J = 8.50 Hz, 1H), 7.34–7.38 (m, 1H), 7.59–7.62 (m,
1
H), 7.96 (br s, 1H), 8.17–8.18 (d, J = 6.29 Hz, 2H),
8.53 (br s, 1H), 8.97 (br s, 1H), 10.74 (s, 1H). ESI-
MS: m/z [M+H] 460.7.
+
+
ESI-MS: m/z [M+H] 474.5.
5
.2.17. (2S,4S)-N-(2-Chlorophenyl)-4-(6-(3-nitroguanidi-
no)hexanamido)pyrrolidine-2-carboxamide hydrochloride
24). White solid, yield: 79%. Mp: 132–134 °C; IR (KBr,
5.2.21. (2S,4S)-N-(2,5-Dichlorophenyl)-4-(6-(3-nitrogua-
nidino)hexanamido)pyrrolidine-2-carboxamide hydrochlo-
(
ride (28). White solid, yield: 71%. Mp: 124–126 °C; IR
ꢀ
1
ꢀ1
cm ) v
3291, v
3052, v 2936, v 2861, v
(KBr, cm ) v 3296–3382, v
1691, 1639, v
3052, v 2936, v
Ar–H CH C@O
1588, vNH 1531, vCH 1404, vN–NO2
NH
Ar–H
CH
CH
C@O
NH
1
1
1
685, 1638, v
1593, vNH 1538, vCH 1442, vN–NO2
Ar,C–C
Ar,C–C
1
1
267. H NMR (DMSO-d ) d 1.22–1.26 (m, 2H), 1.46–
1265. H NMR (DMSO-d ) d 1.22–1.26 (m, 2H), 1.46–
6
6
.51 (m, 4H), 1.88–1.93 (m, 1H), 2.05–2.08 (t,
1.50 (m, 4H), 1.90–1.93 (m, 1H), 2.05–2.08 (m, 2H),
2.75–2.78 (m, 1H), 3.07–3.10 (m, 3H), 3.45–3.48 (m,
1H), 4.32–4.34 (m, 1H), 4.50 (m, 1H), 7.33–7.35 (dd,
J = 2.38, 8.71 Hz, 1H), 7.58–7.59 (d, J = 8.61 Hz, 1H),
7.84 (s, H), 7.90 (br s, 2H), 8.11–8.12 (d, J = 5.49 Hz,
J = 7.48 Hz, 2H), 2.73–2.76 (m, 1H), 3.03–3.06 (t,
J = 9.19 Hz, 1H), 3.11 (br s, 2H), 3.46–3.48 (m, 1H),
4
.32–4.38 (m, 1H), 4.47–4.48 (t, J = 8.00 Hz, 1H),
.26–7.29 (dt, J = 1.52, 7.71 Hz, 1H), 7.37–7.40 (dt,
7