X. Wang, K. Wu, L. Fang et al.
European Journal of Medicinal Chemistry 218 (2021) 113362
131.9, 129.3, 113.3. Anal. Calcd for C13H6ClF5N2O3S: C, 38.93; H, 1.51;
N, 6.99. Found: C, 38.73; H, 1.50; N, 6.97.
4.27; N, 7.89. Found: C, 50.43; H, 4.26; N, 7.91.
4-chloro-N-(2,3-dichlorobenzyl)-3-sulfamoylbenzamide
(X4).
4-chloro-N-(4-(4-methylpiperazin-1-yl)phenyl)-3-
Yield/%: 85.3%; MP: 174.2e177.6 ꢀC; ESI-MS: 392.92 [MþH]þ; 1H
sulfamoylbenzamide (B16). Yield/%: 21.6%; MP: 282.3e285.7 ꢀC; ESI-
NMR (600 MHz, DMSO‑d6)
d
(ppm): 9.41 (t, 1H, J ¼ 6.0 Hz), 8.51 (d,
MS: 409.07 [MþH]þ; 1H NMR (600 MHz, DMSO‑d6)
d
(ppm): 10.46
1H, J ¼ 2.4 Hz), 8.11 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 2.4 Hz), 7.79 (d, 1H,
J ¼ 8.4 Hz), 7.57 (dd, 1H, J1 ¼ 6.6 Hz, J2 ¼ 2.4 Hz), 7.55 (d, 1H,
J ¼ 7.8 Hz), 7.34 (m, 3H), 4.58 (d, 2H, J ¼ 5.4 Hz); 13C NMR (151 MHz,
DMSO‑d6): 165.1, 141.8, 139.3, 134.1, 133.5, 132.3, 132.3, 130.6, 129.7,
128.8,128.7, 128.0, 42.2. Anal. Calcd for C14H11Cl3N2O3S: C, 42.68; H,
2.82; N, 7.11. Found: C, 42.54; H, 2.81; N, 7.14.
(s, 1H), 8.56 (d, 1H, J ¼ 1.2 Hz), 8.16 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 1.8 Hz),
7.79 (d, 1H, J ¼ 8.4 Hz), 7.67 (m, 2H), 7.62 (d, 2H, J ¼ 9.0 Hz), 6.93 (d,
2H, J ¼ 9.0 Hz), 3.10 (t, 4H, J ¼ 4.8 Hz), 2.45 (t, 4H, J ¼ 4.8 Hz), 2.22 (s,
3H); 13C NMR (151 MHz, DMSO‑d6): 163.5, 141.7, 134.5, 133.8, 132.5,
132.2, 131.3, 129.0, 122.3, 116.1, 52.5, 52.0, 48.6. Anal. Calcd for
C
18H21ClN4O3S: C, 52.82; H, 5.19; N, 13.70. Found: C, 52.67; H, 5.18;
N, 13.71.
4-chloro-N-(4-(N-(diaminomethylene)sulfamoyl)phenyl)-3-
4-chloro-N-(2-methoxybenzyl)-3-sulfamoylbenzamide
(X5).
Yield/%: 87.9%; MP: 199.2e202.0 ꢀC; ESI-MS: 414.96 [MþH]þ; 1H
NMR (500 MHz, DMSO‑d6)
d
(ppm): 9.28 (t, 1H, J ¼ 5.5 Hz), 8.50 (d,
sulfamoylbenzamide (B17). Yield/%: 79.1%; MP: 243.8e246.4 ꢀC; ESI-
1H, J ¼ 1.5 Hz), 8.09 (dd, 1H, J1 ¼ 8.5 Hz, J2 ¼ 2.0 Hz), 7.77 (d, 1H,
J ¼ 8.0 Hz), 7.68 (s, 2H), 6.66 (s, 2H), 4.44 (d, 1H, J ¼ 5.5 Hz), 3.76 (s,
6H), 3.64 (s, 3H); 13C NMR (125 MHz, DMSO‑d6): 164.3, 152.8, 141.2,
136.6, 134.8, 133.4, 133.2, 131.6, 131.5, 128., 105.0, 60.0, 55.9, 43.1.
Anal. Calcd for C17H19ClN2O6S: C, 49.17; H, 4.63; N, 6.75. Found: C,
49.03; H, 4.61; N, 6.77.
MS: 431.99 [MþH]þ; 1H NMR (600 MHz, DMSO‑d6)
d (ppm): 10.78
(s, 1H), 8.53 (d, 1H, J ¼ 2.4 Hz), 8.19 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 1.8 Hz),
7.84 (m, 3H), 7.75 (m, 4H), 6.69 (br-s, 4H); 13C NMR (151 MHz,
DMSO‑d6): 164.5, 158.7, 141.8, 141.8, 140.2, 134.4, 134.1, 132.7, 132.4,
129.2, 127.1, 120.5. Anal. Calcd for C14H14ClN5O5S2: C, 38.94; H, 3.27;
N, 16.22. Found: C, 38.90; H, 3.26; N, 16.16.
3-(N-acryloylsulfamoyl)-4-chloro-N-(3, 4, 5-trimethoxyphenyl)
benzamide (Y1). Yield/%: 55.9%; MP: 174.9e177.0 ꢀC; ESI-MS: 455.20
4-chloro-3-sulfamoyl-N-(3-sulfamoylphenyl)benzamide
(B18).
Yield/%: 79.5%; MP: 171.5e173.3 ꢀC; ESI-MS: 389.92 [MþH]þ; 1H
[MþH]þ; 1H NMR (600 MHz, DMSO‑d6)
d (ppm): 10.56 (s, 1H), 8.58
NMR (600 MHz, DMSO‑d6)
d
(ppm): 10.83 (s, 1H), 8.56 (d, 1H,
(d,1H, J ¼ 1.8 Hz), 8.22 (d,1H, J ¼ 6.6 Hz), 7.71 (d,1H, J ¼ 6.6 Hz), 7.25
(s, 2H), 6.05 (m, 2H), 5.62 (s, 1H), 3.77 (s, 6H), 3.64 (s, 3H), (The
chemical shift of SO2NHCO was not shown); 13C NMR (125 MHz,
DMSO‑d6): 163.6, 162.9, 152.6, 137.0, 134.6, 134.2, 133.9, 133.6, 133.4,
131.9, 131.4, 98.6, 60.1, 55.8. Anal. Calcd for C19H19ClN2O7S: C, 50.12;
H, 4.22; N, 6.16. Found: C, 49.97; H, 4.22; N, 6.14.
J ¼ 2.4 Hz), 8.32 (d, 1H, J ¼ 1.2 Hz), 8.21 (dd, 1H, J1 ¼ 8.4 Hz,
J2 ¼ 2.4 Hz), 7.97 (m, 1H), 7.86 (d, 1H, J ¼ 8.4 Hz), 7.77 (s, 2H), 7.57
(m, 2H), 7.41 (s, 2H); 13C NMR (151 MHz, DMSO‑d6): 164.4, 145.2,
141.8, 139.7, 134.4, 134.0, 132.7, 132.4, 130.1, 129.2, 124.0, 121.8, 118.1.
Anal. Calcd for C13H12ClN3O5S2: C, 40.02; H, 3.11; N, 10.77. Found: C,
39.95; H, 3.10; N, 10.74.
4-chloro-3-(N-methacryloylsulfamoyl)-N-(3,4,5-
4-chloro-N-(2-chloro-4-nitrophenyl)-3-sulfamoylbenzamide
trimethoxyphenyl)benzamide
(Y2).
Yield/%:
44.3%;
MP:
(B19). Yield/%: 28.6%; MP: 246.6e248.1 ꢀC; ESI-MS: 390.01 [MþH]þ;
184.8e187.8 ꢀC; ESI-MS: 469.23 [MþH]þ; 1H NMR (600 MHz,
1H NMR (600 MHz, DMSO‑d6)
d
(ppm): 10.72 (s, 1H), 8.57 (d, 1H,
DMSO‑d6) d (ppm): 12.69 (br-s, 1H), 10.58 (s, 1H), 8.59 (s, 1H), 8.23
J ¼ 1.8 Hz), 8.43 (d, 1H, J ¼ 2.4 Hz), 8.28 (dd, 1H, J1 ¼ 9.0 Hz,
J2 ¼ 2.4 Hz), 8.20 (dd, 1H, J1 ¼ 7.8 Hz, J2 ¼ 1.8 Hz), 8.00 (d, 1H,
J ¼ 9.0 Hz), 7.88 (d, 1H, J ¼ 7.8 Hz), 7.79 (s, 2H); 13C NMR (151 MHz,
DMSO‑d6): 164.4, 145.6, 141.9, 141.6, 134.9, 133.0, 132.9, 132.6, 129.4,
129.3,128.1, 125.6,123.6. Anal. Calcd for C13H9Cl2N3O5S: C, 39.98; H,
2.33; N, 10.76. Found: C, 39.76; H, 2.33; N, 10.76.
(m, 1H), 7.74 (m, 1H), 7.25 (s, 2H), 5.83 (m, 1H), 5.49 (m, 1H), 3.77 (s,
6H), 3.64 (s, 3H), 1.75 (s, 3H); 13C NMR (125 MHz, DMSO‑d6): 163.6,
162.9, 153.2, 152.6, 137.0, 134.6, 134.0, 133.6, 133.5, 131.9, 131.4,
115.6, 106.8, 98.6, 60.1, 56.2, 20.0. Anal. Calcd for C20H21ClN2O7S: C,
51.18; H, 4.52; N, 5.97. Found: C, 51, 04; H, 4.52; N, 5.94.
4-chloro-3-(N-(3-methylbut-2-enoyl)sulfamoyl)-N-(3,4,5-
4-chloro-N-(2-methoxybenzyl)-3-sulfamoylbenzamide
(X1).
trimethoxyphenyl)benzamide
(Y3).
Yþield/%:
41.6%;
MP:
Yield/%: 29.7%; MP: 188.2e191.5 ꢀC; ESI-MS: 355.09 [MþH]þ; 1H
194.9e196.2 ꢀC; ESI-MS: 483.19 [MþH] ; 1H NMR (600 MHz,
NMR (600 MHz, DMSO‑d6)
d
(ppm): 9.16 (t, 1H, J ¼ 5.4 Hz), 8.50 (d,
DMSO‑d6) d (ppm): 12.4 (br-s, 1H), 10.51 (s, 1H), 8.64 (d, 1H,
1H, J ¼ 2.4 Hz), 8.10 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 1.8 Hz), 7.77 (d, 1H,
J ¼ 8.4 Hz), 7.71 (s, 2H), 7.23 (m, 1H), 7.17 (d, 1H, J ¼ 7.2 Hz), 7.00 (d,
1H, J ¼ 7.8 Hz), 6.91 (t,1H, J ¼ 7.2 Hz), 4.46 (d, 2H, J ¼ 6.0 Hz), 3.82 (s,
3H); 13C NMR (151 MHz, DMSO‑d6): 165.0, 157.2, 141.7, 133.9, 133.8,
132.3, 132.2, 128.8, 128.7, 128.0, 127.0, 120.7, 111.1, 56.0, 38.5. Anal.
Calcd for C15H15ClN2O4S: C, 50.73; H, 4.27; N, 7.89. Found: C, 50.51;
H, 4.28; N, 7.88.
J ¼ 2.4 Hz), 8.25 (dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 2.4 Hz), 7.87 (d, 1H,
J ¼ 8.4 Hz), 7.19 (s, 2H), 5.80 (s, 1H), 3.78 (s, 6H), 3.65 (s, 3H), 1.97 (s,
3H), 1.84 (s, 3H); 13C NMR (125 MHz, DMSO‑d6): 163.6, 162.9, 153.2,
152.6, 137.0, 134.6, 134.2, 133.9, 133.6, 133.4, 131.9, 131.5, 131.4, 98.6,
60.1, 55.8, 27.3, 20.0. Anal. Calcd for C21H23ClN2O7S: C, 52.18; H,
4.81; N, 5.80. Found: C, 52.02; H, 4.80; N, 5.82.
3-(N-acetylsulfamoyl)-4-chloro-N-(3, 4, 5-trimethoxyphenyl)ben-
4-chloro-N-(3-methoxybenzyl)-3-sulfamoylbenzamide
þ(X2).
zamide (Y4). Yield/%: 49.1%; MP: 210.0e211.5 ꢀC; ESI-MS: 443.21
Yield/%: 22.8%; MP: 189.1e191.0 ꢀC; ESI-MS: 355.16 [MþH] ; 1H
[MþH]þ; 1H NMR (600 MHz, DMSO‑d6)
d (ppm): 12.66 (br-s, 1H),
NMR (600 MHz, DMSO‑d6)
d
(ppm): 9.32 (t, 1H, J ¼ 6.0 Hz), 8.49 (d,
10.50 (s, 1H), 8.61 (d, 1H, J ¼ 2.4 Hz), 8.23 (dd, 1H, J1 ¼ 8.4 Hz,
J2 ¼ 1.8 Hz), 7.88 (d, 1H, J ¼ 8.4 Hz), 7.19 (s, 2H), 3.78 (s, 6H), 3.65 (s,
3H), 1.98 (s, 3H); 13C NMR (125 MHz, DMSO‑d6): 169.1, 162.9, 152.6,
134.6, 134.2, 133.9, 133.7, 133.5, 131.9, 131.3, 98.6, 60.1, 55.8.23.1.
Anal. Calcd for C18H19ClN2O7S: C, 48.77; H, 4.33; N, 6.32. Found: C,
48.67; H, 4.32; N, 6.33.
1H, J ¼ 1.8 Hz), 8.08 (dd, 1H, J1 ¼ 7.8 Hz, J2 ¼ 1.8 Hz), 7.77 (d, 1H,
J ¼ 8.4 Hz), 7.71 (s, 2H), 6.81 (m, 4H), 4.46 (d, 2H, J ¼ 6.0 Hz), 3.73 (s,
3H); 13C NMR (151 MHz, DMSO‑d6): 164.9, 161.7, 159.9, 141.7, 141.4,
133.9, 132.3, 132.1, 130.0, 128.8, 120.0, 113.7, 112.8, 55.6, 43.4. Anal.
Calcd for C15H15ClN2O4S: C, 50.73; H, 4.27; N, 7.89. Found: C, 50.35;
H, 4.26; N, 7.89.
4-chloro-3-(N-propionylsulfamoyl)-N-(3,4,5-trimethoxyphenyl)
4-chloro-N-(4-methoxybenzyl)-3-sulfamoylbenzamide
(X3).
benzamide (Y5). Yield/%: 33.9%; MP: 217.9e219.2 ꢀC; ESI-MS: 457.24
Yield/%: 82.2%; MP: 184.9e186.2 ꢀC; ESI-MS: 355.09 [MþH]þ; 1H
[MþH]þ; 1H NMR (600 MHz, DMSO‑d6)
d (ppm): 12.61 (br-s, 1H),
NMR (600 MHz, DMSO‑d6)
d
(ppm): 9.27 (t, 1H, J ¼ 5.4 Hz), 8.48 (d,
10.50 (s, 1H), 8.62 (d, 1H, J ¼ 1.8 Hz), 8.24 (dd, 1H, J1 ¼ 8.4 Hz,
J2 ¼ 1.8 Hz), 7.86 (d, 1H, J ¼ 8.4 Hz), 7.19 (s, 2H), 3.78 (s, 6H), 3.65 (s,
3H), 2.27 (q, 2H, J ¼ 7.8 Hz), 0.90 (t, 3H, J ¼ 7.8 Hz); 13C NMR
(125 MHz, DMSO‑d6): 172.8, 162.9, 152.6, 134.7, 134.2, 133.8, 133.6,
133.3, 131.8, 131.3, 98.6, 60.1, 55.8, 28.9, 8.4. Anal. Calcd for
1H, J ¼ 1.8 Hz), 8.06 (dd, 1H, J1 ¼ 7.8 Hz, J2 ¼ 1.8 Hz), 7.76 (d, 1H,
J ¼ 8.4 Hz), 7.70 (s, 2H), 7.25 (d, 2H, J ¼ 8.4 Hz), 6.89 (d, 2H,
J ¼ 8.4 Hz), 4.41 (d, 2H, J ¼ 5.4 Hz), 3.72 (s, 3H); 13C NMR (151 MHz,
DMSO‑d6): 164.7, 161.5, 158.9, 141.7, 134.0, 133.8, 132.3, 132.1, 131.8,
131.5, 129.3, 128.8, 114.3. Anal. Calcd for C15H15ClN2O4S: C, 50.73; H,
C
19H21ClN2O7S: C, 49.90; H, 4.64; N, 6.13. Found: C, 49.87; H, 4.64;
12