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S. Yrjola et al. / European Journal of Medicinal Chemistry 107 (2016) 119e132
129
(DMSO-d6):
d
3.98 (2H, d, J ¼ 6.1 Hz), 7.06 (2H, d, J ¼ 8.3 Hz), 7.45
7.45 (1H, t, J ¼ 7.6 Hz), 7.53 (2H, t, J ¼ 7.3 Hz), 7.78 (2H, m), 7.80 (2H,
d, J ¼ 8.8 Hz), 7.86 (2H, d, J ¼ 8.8 Hz), 7.98 (2H, d, J ¼ 8.8 Hz), 8.09
(2H, d, J ¼ 8.8 Hz), 10.47 (1H, s), 11.72 (1H, s), 12.76 (1H, s); 13C NMR
(1H, t, J ¼ 7.3 Hz), 7.55 (2H, t, J ¼ 7.6 Hz), 7.65 (2H, d, J ¼ 8.3 Hz), 7.78
(2H, d, J ¼ 7.3 Hz), 7.82 (2H, d, J ¼ 8.7 Hz), 7.87 (2H, d, J ¼ 8.4 Hz),
7.96 (2H, d, J ¼ 8.7 Hz), 8.11 (2H, d, J ¼ 8.4 Hz), 8.20 (1H, br t,
J ¼ 6.2 Hz), 11.74 (1H, br s), 12.80 (1H, br s); 13C NMR (DMSO-d6):
(DMSO-d6):
d 121.6, 124.2, 126.6, 127.0, 127.4, 128.2, 128.5, 129.1,
129.2, 129.5, 130.7, 136.0, 136.6, 138.7, 142.0, 144.6, 167.7, 179.2; ESI-
MS 519.95 [MꢃH]-; Anal. Calcd for C26H20ClN3O3S2 ꢁ 0.3H2O: C
59.21, N 7.97, H 3.94, S 12.16; found: C 58.82, N 7.88, H 3.85, S 12.04.
d
45.6, 93.0, 124.2, 126.6, 127.0, 127.2, 128.5, 129.1, 129.5, 129.9,
130.8, 137.0, 137.6, 137.7, 138.7, 141.5, 144.6, 167.8, 179.3; ESI-MS
625.75 [MꢃH]-; Anal. Calcd for C27H22IN3O3S2: C 51.68, N 6.70, H
3.53, S 10.22; found: C 51.96, N 6.49, H 3.42, S 9.99.
4.6.4.44. N-((4-(N-(4-butylphenyl)sulfamoyl)phenyl)carbamo-
thioyl)-[1,10-biphenyl]-4-carboxamide (17i). From 14i (0.75 g,
2.5 mmol) with general procedure C. Light yellow solid (0.36 g,
4.6.4.39. N-((4-(N-(4-Methylbenzyl)sulfamoyl)phenyl)carbamo-
thioyl)-[1,10-biphenyl]-4-carboxamide (17d). From 14d (0.40 g,
1.4 mmol) with general procedure C. White solid (60 mg, 8%). 1H
27%). 1H NMR (DMSO-d6):
d
0.86 (3H, t, J ¼ 7.4 Hz), 1.24 (2H, sxt,
J ¼ 7.6 Hz), 1.47 (2H, m), 2.46 (2H, t, J ¼ 7.6 Hz), 7.01 (2H, d,
J ¼ 8.5 Hz), 7.06 (2H, d, J ¼ 8.2 Hz), 7.44 (1H, t, J ¼ 7.3 Hz), 7.52 (2H, t,
J ¼ 7.3 Hz), 7.77 (4H, m), 7.85 (2H, d, J ¼ 8.5 Hz), 7.94 (2H, d,
J ¼ 8.7 Hz), 8.09 (2H, d, J ¼ 8.5 Hz), 10.16 (1H, s), 11.71 (1H, s), 12.75
NMR (DMSO-d6):
d
2.26 (3H, s), 3.97 (2H, d, J ¼ 6.3 Hz), 7.11 (4H, m),
7.45 (1H, t, J ¼ 7.4 Hz), 7.53 (2H, t, J ¼ 7.8 Hz), 7.78 (2H, d, J ¼ 7.4 Hz),
7.83 (2H, d, J ¼ 8.7 Hz), 7.87 (2H, d, J ¼ 8.7 Hz), 7.96 (2H, d,
J ¼ 8.8 Hz), 8.11 (2H, d, J ¼ 8.7 Hz), 11.74 (1H, s), 12.79 (1H, s); 13C
(1H, s); 13C NMR (DMSO-d6):
d 13.7, 21.7, 33.0, 34.1, 120.5, 124.0,
NMR (DMSO-d6):
d
20.7, 45.9, 124.2, 126.6, 127.0, 127.2, 127.6, 128.5,
126.6, 127.0, 127.4, 128.5, 128.9, 129.1, 129.5, 130.7, 135.1, 136.5,
138.3, 138.7, 141.8, 144.6, 167.7, 179.2; ESI-MS 541.98 [MꢃH]-; Anal.
Calcd for C30H29N3O3S2: C 66.27, N 7.73, H 5.38, S 11.79; found: C
65.94, N 7.98, H 5.43, S 11.28.
128.8, 129.1, 129.5, 130.8, 134.5, 136.3, 137.8, 138.7, 141.4, 144.6,
167.8, 179.3; ESI-MS 513.96 [MꢃH]-; Anal. Calcd for C28H25N3O3S2:
C 65.22, N 8.15, H 4.89, S 12.44; found: C 65.67, N 7.87, H 4.68, S
11.34.
4.6.4.45. N-((4-(N-Phenethylsulfamoyl)phenyl)carbamothioyl)-[1,10-
biphenyl]-4-carboxamide (17j). From 14j (0.39 g, 1.4 mmol) with
general procedure C. White solid (0.07 g, 10%). 1H NMR (DMSO-d6):
4.6.4.40. N-((4-(N-(4-Methoxybenzyl)sulfamoyl)phenyl)carbamo-
thioyl)-[1,10-biphenyl]-4-carboxamide (17e). From 14e (0.22 g,
0.8 mmol) with general procedure C. White solid (0.14 g, 35%). 1H
d
2.70 (2H, t, J ¼ 7.4 Hz), 3.00 (2H, dt, J ¼ 7.6, 5.3 Hz), 7.16e7.22 (3H,
NMR (DMSO-d6):
d
3.72 (3H, s), 3.95 (2H, d, J ¼ 6.3 Hz), 6.84 (2H, d,
m), 7.28 (2H, t, J ¼ 7.3 Hz), 7.45 (1H, t, J ¼ 7.6 Hz), 7.53 (2H, t,
J ¼ 7.6 Hz), 7.75e7.80 (3H, m), 7.82 (2H, d, J ¼ 8.8 Hz), 7.87 (2H, d,
J ¼ 8.5 Hz), 7.97 (2H, d, J ¼ 8.5 Hz), 8.11 (2H, d, J ¼ 8.5 Hz), 11.76 (1H,
J ¼ 8.7 Hz), 7.15 (2H, d, J ¼ 8.8 Hz), 7.45 (1H, t, J ¼ 7.3 Hz), 7.53 (2H, t,
J ¼ 7.9 Hz), 7.78 (2H, d, J ¼ 7.4 Hz), 7.83 (2H, d, J ¼ 8.7 Hz), 7.87 (2H,
d, J ¼ 8.5 Hz), 7.96 (2H, d, J ¼ 8.8 Hz), 8.08 (1H, t, J ¼ 6.3 Hz), 8.11 (2H,
s), 12.79 (1H, s); 13C NMR (DMSO-d6):
d 35.3, 44.1, 124.3, 126.2,
d, J ¼ 8.5 Hz), 11.74 (1H, s), 12.79 (1H, s); 13C NMR (DMSO):
d
45.7,
126.6, 127.0, 127.1, 128.3,128.4,128.7, 129.1, 129.5,130.8, 137.4, 138.7,
55.0, 113.6, 124.2, 126.6, 127.0, 127.2, 128.5, 128.9, 129.1, 129.4, 129.5,
130.8, 137.8, 138.7, 141.3, 144.6, 158.4, 167.8, 179.3; ESI-MS 529.95
[MꢃH]-; Anal. Calcd for C28H25N3O4S2: C 63.26, N 7.90, H 4.74, S
12.06; found: C 62.89, N 7.87, H 4.36, S 12.48.
141.4, 144.6, 167.8, 179.3; ESI-MS 514.09 [MꢃH]-; Anal. Calcd for
C28H25N3O3S2: C 65.22, N 8.15, H 4.89, S 12.44; found: C 65.14, N
8.22, H 5.02, S 10.91.
4.6.4.46. N-((4-(Phenethylcarbamoyl)phenyl)carbamothioyl)-[1,10-
biphenyl]-4-carboxamide (17k). From 14k (0.40 g, 1.7 mmol) with
general procedure C. Light yellow solid (0.04 g, 8%). 1H NMR
4.6.4.41. N-((4-(Benzylcarbamoyl)phenyl)carbamothioyl)-[1,10-
biphenyl]-4-carboxamide (17f). From 14f (0.40 g, 1.8 mmol) with
general procedure C. White solid (0.29 g, 35%). 1H NMR (DMSO-d6):
(DMSO-d6):
d
2.86 (2H, t, J ¼ 7.5 Hz), 3.50 (2H, dt, J ¼ 7.9, 6.5), 7.21
d
4.50 (2H, d, J ¼ 6.2 Hz), 7.25 (1H, m), 7.34 (4H, m), 7.45 (1H, t,
(1H, t, J ¼ 7.5 Hz), 7.24e7.34 (4H, m), 7.45 (1H, t, J ¼ 7.4 Hz), 7.53 (2H,
t, J ¼ 7.6 Hz), 7.78 (2H, d, J ¼ 7.4 Hz), 7.84e7.89 (2H, m), 8.97 (2H, d,
J ¼ 8.4 Hz), 8.02 (2H, d, J ¼ 8.6 Hz), 8.10 (2H, d, J ¼ 8.4 Hz), 8.59 (1H,
J ¼ 7.5 Hz), 7.53 (2H, t, J ¼ 7.6 Hz), 7.78 (2H, d, J ¼ 7.3 Hz), 7.86 (4H, d,
J ¼ 8.5 Hz), 7.95 (2H, d, J ¼ 8.5 Hz), 8.10 (2H, d, J ¼ 8.5 Hz), 9.07 (1H,
t, J ¼ 6.1 Hz),11.68 (1H, s), 12.77 (1H, s); 13C NMR (DMSO-d6):
d
42.6,
t, J ¼ 5.5 Hz), 11.68 (1H, s), 12.76 (1H, s); 13C NMR (DMSO-d6):
d 35.1,
123.6, 126.6, 126.7, 127.0, 127.2, 127.8, 128.3, 128.5, 129.1, 129.5,
130.8, 131.8, 138.7, 139.7, 140.5, 144.6, 165.5, 167.9, 179.1; ESI-MS
466.12 [MþH]þ; Anal. Calcd for C28H23N3O2S: C 72.24, N 9.03, H
4.98, S 6.89; found: C 72.33, N 8.92, H 4.92, S 7.05.
40.9, 123.5, 126.1, 126.6, 127.0, 127.6, 128.3, 128.5, 128.6, 129.1, 129.5,
130.8, 132.1, 138.7, 139.5, 140.4, 144.6, 165.4, 167.9, 179.0; ESI-MS
478.02 [MꢃH]-; Anal. Calcd for C29H25N3O2S ꢁ 0.2H2O: C 72.09, N
8.70, H 5.30, S 6.64; found: C 71.65, N 8.74, H 4.97, S 6.19.
4.6.4.42. N-((4-(N-Phenylsulfamoyl)phenyl)carbamothioyl)-[1,10-
biphenyl]-4-carboxamide (17g). From 14g (0.22 g, 0.9 mmol) with
general procedure C. Light yellow solid (40 mg, 9%). 1H NMR
4.6.4.47. N-((4-(N-(Furan-2-ylmethyl)sulfamoyl)phenyl)carbamo-
thioyl)-[1,10-biphenyl]-4-carboxamide (17l). From 14l (0.41 g,
1.6 mmol) with general procedure C. Light yellow solid (0.09 g, 11%).
(DMSO-d6):
d
7.03 (1H, tt, J ¼ 7.4.1.1 Hz), 7.12 (2H, dd, J ¼ 8.6,1.1 Hz),
1H NMR (DMSO-d6):
d
4.04 (2H, d, J ¼ 6.0 Hz), 6.20 (1H, d,
7.25 (2H, dd, J ¼ 8.6, 7.5 Hz), 7.44 (1H, t, J ¼ 7.3 Hz), 7.52 (2H, t,
J ¼ 7.6 Hz), 7.77 (2H, d, J ¼ 7.2 Hz), 7.79 (2H, d, J ¼ 8.8 Hz), 7.85 (2H,
d, J ¼ 8.4 Hz), 7.95 (2H, d, J ¼ 8.8 Hz), 8.08 (2H, d, J ¼ 8.4 Hz), 10.30
J ¼ 3.4 Hz), 6.32 (1H, dd, J ¼ 3.4, 1.6 Hz), 7.45 (1H, t, J ¼ 7.4 Hz), 7.53
(2H, t, J ¼ 7.7 Hz), 7.77e7.82 (m, 3H), 7.84 (2H, d, J ¼ 8.4 Hz), 7.87
(2H, d, J ¼ 8.4 Hz), 7.95 (2H, d, J ¼ 8.5 Hz), 8.11 (2H, d, J ¼ 8.5 Hz),
8.22 (1H, t, J ¼ 6.3 Hz), 11.78 (1H, s), 12.79 (1H, s). 13C NMR (DMSO-
(1H, s), 11.70 (1H, s), 12.74 (1H, s); 13C NMR (DMSO-d6):
d 120.0,
124.1, 126.6, 127.0, 127.4, 128.5, 129.1, 129.2, 129.5(x2C), 130.7, 136.4,
137.6, 138.7, 141.9, 144.6, 167.7, 179.2; ESI-MS 485.99 [MꢃH]-; Anal.
Calcd for C26H21N3O3S2 ꢁ 0.15H2O: C 63.69, N 8.57, H 4.38, S 13.08;
found: C 63.28, N 8.39, H 4.45, S 12.45.
d6): d ~41 (overlap with the solvent), 108.0, 110.4, 124.1, 126.6, 127.0,
127.1, 128.5, 129.1, 129.5, 130.8, 137.7, 138.7, 141.3, 142.5, 144.6, 150.5,
167.8, 179.3; ESI-MS 492.02 [MþH]þ; Anal. Calcd for C25H21N3O4S2:
C 61.92, N 8.23, H 4.75, S 12.56; found: C 62.32, N 8.36, H 4.45, S
12.58. Purity (ꢀ95%) was also determined by HPLC. Eluent: water/
acetonitrile (40:60).
4.6.4.43. N-((4-(N-(4-Chlorophenyl)sulfamoyl)phenyl)carbamo-
thioyl)-[1,10-biphenyl]-4-carboxamide (17h). From 14h (0.62 g,
2.2 mmol) with general procedure C. White solid (0.55 g, 48%). 1H
4.6.4.48. N-((4-(N-(2-(1H-Indol-3-yl)ethyl)sulfamoyl)phenyl)carba-
mothioyl)-[1,10-biphenyl]-4-carboxamide (17m). From 14m (0.43 g,
NMR (DMSO-d6):
d
7.14 (2H, d, J ¼ 8.8 Hz), 7.33 (2H, d, J ¼ 8.8 Hz),