JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
1203
HRMS (ESI) m/z: [M þ H]þ calculated for C17H18N5O4S 388.1074, 1H), 8.10 (dd, J ¼ 8.3, 2.2 Hz, 1H), 7.98–7.91 (m, 2H), 7.78 (d,
found 388.1082.
J ¼ 8.3 Hz, 1H), 7.70 (s, 2H), 7.47–7.39 (m, 2H), 4.62 (d, J ¼ 5.6 Hz,
2H).13C NMR (125 MHz, DMSO) d 164.76, 163.03, 146.35, 141.64,
133.76, 133.58, 132.07, 128.78, 122.79 (d, J ¼ 8.8 Hz), 121.98,
2.2.5.5. N-((1–(2,3-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-3-
117.25, 117.07, 35.46. HRMS (ESI) m/z: [M þ H]þ calculated for
sulfamoylbenzamide (6g). White solid; yield: 86%, m.p: 205–206 ꢀC;
1H NMR (500 MHz, DMSO) d 9.30 (t, J ¼ 5.5 Hz, 1H), 8.36 (s, 1H), 8.27
C16H14 ClFN5O3S 410.0484, found 410.0492.
(s, 1H), 8.09 (t, J ¼ 9.4 Hz, 1H), 7.97 (d, J ¼ 7.8 Hz, 1H), 7.68 (t,
J ¼ 7.8 Hz, 1H), 7.44 (s, 2H), 7.39 (d, J¼ 7.6 Hz, 1H), 7.28 (t, J ¼ 7.7 Hz, 2.2.6.1. 4-Chloro-3-sulfamoyl-N-((1–(4-(trifluoromethyl)phenyl)-1H-
1H), 7.20 (d, J ¼ 7.8 Hz, 1H), 4.65 (d, J ¼ 5.5 Hz, 2H), 2.34 (s, 3H), 1.96
1,2,3-triazol-4-yl)methyl)benzamide(6m). White solid, yield: 92%,
m.p: 178–180 ꢀC; 1H NMR (500 MHz, DMSO) d 9.42 (t, J ¼ 5.6 Hz,
(s, 3H).13C NMR (125 MHz, DMSO) d 165.59, 145.21, 144.91, 138.91,
136.95, 135.40, 132.64, 131.48, 130.78, 129.57, 128.69, 126.62, 125.37,
1H), 8.87 (s, 1H), 8.52 (d, J ¼ 2.1 Hz, 1H), 8.18 (d, J ¼ 8.5 Hz, 2H),
124.36, 35.42, 20.34, 14.40. HRMS (ESI) m/z: [Mþ H]þ calculated for
8.10 (dd, J ¼ 8.3, 2.2 Hz, 1H), 8.03–7.92 (m, 2H), 7.82–7.74 (m, 1H),
C18H20N5O3S 386.1281, found 386.1287.
7.70 (s, 2H), 4.64 (d, J ¼ 5.5 Hz, 2H).13C NMR (125 MHz, DMSO) d
164.79, 146.78, 141.65, 139.91, 133.80, 133.54, 132.08, 128.78,
127.64, 122.00, 120.89, 35.44. HRMS (ESI) m/z: [M þ H]þ calculated
2.2.5.6. N-((1–(2,4-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-3-
sulfamoylbenzamide (6h). White solid, yield: 89%, m.p: 189–191 ꢀC;
1H NMR (500 MHz, DMSO) d 9.29 (t, J ¼ 5.4 Hz, 1H), 8.35 (d,
J ¼ 1.5 Hz, 1H), 8.29 (s, 1H), 8.10 (d, J ¼ 7.8 Hz, 1H), 7.97 (d, J ¼ 8.3 Hz,
1H), 7.68 (t, J¼ 7.8 Hz, 1H), 7.43 (s, 2H), 7.27 (d, J ¼ 7.7 Hz, 2H), 7.19
(d, J ¼ 8.0 Hz, 1H), 4.64 (d, J ¼ 5.5 Hz, 2H), 2.36 (s, 3H), 2.11 (s, 3H).
13C NMR (125 MHz, DMSO) d 165.56, 145.17, 144.91, 139.78, 135.39,
134.46, 133.12, 132.23, 130.78, 129.57, 128.69, 127.83, 126.18, 125.37,
125.06, 35.41, 21.07, 17.82. HRMS (ESI) m/z: [Mþ H]þ calculated for
C18H20N5O3S 386.1281, found 386.1288.
for C17H14ClF3N5O3S 460.0452, found 460.0343.
2.2.6.2. 4-Fluoro-N-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-3-sulfa-
moylbenzamide (6n). White solid, yield: 87%, m.p: 192–194 ꢀC; 1H
NMR (500 MHz, DMSO) d 9.35 (t, J ¼ 5.3 Hz, 1H), 8.70 (s, 1H), 8.37
(dd, J ¼ 6.9, 2.0 Hz, 1H), 8.24–8.14 (m, 1H), 7.90 (d, J ¼ 7.8 Hz, 2H),
7.76 (s, 2H), 7.64–7.52 (m, 3H), 7.48 (t, J ¼ 7.4 Hz, 1H), 4.63 (d,
J ¼ 5.5 Hz, 2H).13C NMR (125 MHz, DMSO) d 164.65, 146.36, 137.16,
133.81 (d, J ¼ 9.6 Hz), 132.11 (d, J ¼ 15.0 Hz), 131.00, 130.34, 129.03,
128.65, 121.71, 120.45, 117.97–117.71 (m), 117.60 (d, J ¼ 22.3 Hz),
35.48. HRMS (ESI) m/z: [M þ H]þ calculated for C16H15FN5O3S
376.0874, found 376.0881.
2.2.5.7. 4-Chloro-N-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-3-sulfa-
moylbenzamide (6i). White solid, yield: 83%, m.p: 199–201 ꢀC; 1H
NMR (500 MHz, DMSO) d 9.38 (t, J ¼ 5.5 Hz, 1H), 8.70 (s, 1H), 8.51 (d,
J ¼ 2.1 Hz, 1H), 8.10 (dd, J ¼ 8.3, 2.2Hz, 1H), 7.90 (dd, J ¼ 8.5, 0.9 Hz,
2H), 7.76 (t, J ¼ 10.0Hz, 1H), 7.69 (s, 2H), 7.59 (dd, J ¼ 10.8, 5.0 Hz,
2H), 7.47 (dd, J ¼ 17.5, 10.1 Hz, 1H), 4.63 (d, J ¼ 5.5Hz, 2H).13C NMR
(125 MHz, DMSO) d 164.77, 146.28, 141.63, 137.16, 133.68 (d,
J ¼ 19.8 Hz), 132.08, 130.34, 129.04, 128.79, 121.73, 120.45, 35.49.
HRMS (ESI) m/z: [M þ H]þ calculated for C16H15ClN5O3S 392.0579,
found 392.0586.
2.2.6.3.
4-Fluoro-N-((1–(4-methoxyphenyl)-1H-1,2,3-triazol-4-
yl)methyl)-3-sulfamoylbenzamide (6o). White solid, yield: 85%,m.p:
209–211 ꢀC; 1H NMR (500 MHz, DMSO) d 9.33 (t, J ¼ 5.4 Hz, 1H),
8.59 (s, 1H), 8.37 (dd, J ¼ 7.0, 2.2 Hz, 1H), 8.18 (ddd, J ¼ 8.4, 4.5,
2.3 Hz, 1H), 7.83–7.78 (m, 2H), 7.76 (s, 2H), 7.59–7.51 (m, 1H),
7.16–7.08 (m, 2H), 4.61 (d, J ¼ 5.5 Hz, 2H), 3.82 (s, 3H).13C NMR
(125 MHz, DMSO) d 164.63, 159.67, 146.08, 133.81 (d, J ¼ 9.3 Hz),
132.10 (d, J ¼ 15.0 Hz), 130.99 (d, J ¼ 3.5 Hz), 130.61, 128.64, 122.10,
121.68, 117.69, 117.52, 115.34, 56.03, 35.48. HRMS (ESI) m/z:
[M þ H]þ calculated for C17H17FN5O4S 406.0980, found 406.0988.
2.2.5.8.
4-Chloro-3-sulfamoyl-N-((1–(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazol-4-yl)methyl)-benzamide (6j). White solid, yield: 95%,
m.p: 249–251 ꢀC; 1H NMR (500 MHz, DMSO) d 9.41 (t, J ¼ 5.5 Hz,
1H), 8.73 (s, 1H), 8.51 (d, J ¼ 2.0 Hz, 1H), 8.10 (dd, J ¼ 8.3, 2.1 Hz,
1H), 7.77 (d, J ¼ 8.3 Hz, 1H), 7.69 (s, 2H), 7.20 (s, 2H), 4.63 (d,
J ¼ 5.5 Hz, 2H), 3.87(s, 6H), 3.71 (s, 3H).13C NMR (125 MHz, DMSO)
d 164.72, 154.01, 146.06, 141.66, 137.89, 133.80, 133.57, 133.06,
132.09 (d, J ¼ 4.4 Hz), 128.79, 122.05, 98.59, 60.68, 56.82, 35.45.
HRMS (ESI) m/z: [M þ H]þ calculated for C19H21ClN5O6S 482.0896,
found 482.0899.
2.2.6.4. 4-Fluoro-3-sulfamoyl-N-((1–(4-(trifluoromethyl)phenyl)-1H-
1,2,3-triazol-4-yl)methyl)benzamide (6p). White solid, yield: 79%,
m.p: 157–158 ꢀC; 1H NMR (500 MHz, DMSO) d 9.38 (t, J ¼ 5.6 Hz,
1H), 8.87 (s, 1H), 8.37 (dd, J ¼ 7.0, 2.3 Hz, 1H), 8.23–8.14 (m, 3H),
7.96 (t, J ¼ 9.9 Hz, 2H), 7.76 (s, 2H), 7.55 (dt, J ¼ 18.9, 9.5 Hz, 1H),
4.64 (d, J ¼ 5.6 Hz, 2H). 13C NMR (125 MHz, DMSO) d 164.67,
146.85, 139.91, 133.81 (d, J ¼ 9.3 Hz), 132.13 (d, J ¼ 15.0 Hz), 130.92
(d, J ¼ 3.4 Hz), 129.20, 128.94, 128.64, 127.65 (d, J ¼ 3.9 Hz), 121.98,
120.89, 117.94–117.77 (m), 117.63 (d, J ¼ 22.1 Hz), 35.43. HRMS
(ESI) m/z: [M þ H]þ calculated for C17H14F4N5O3S 444.0748,
found 444.0757.
2.2.5.9.
4-Chloro-N-((1–(4-methoxyphenyl)-1H-1,2,3-triazol-4-
yl)methyl)-3-sulfamoylbenzamide(6k). White solid, yield: 90%, m.p:
172–174 ꢀC; 1H NMR (500 MHz, DMSO) d 9.37 (t, J ¼ 5.5 Hz, 1H),
8.59 (s, 1H), 8.51 (d, J ¼ 2.1 Hz, 1H), 8.09 (dd, J ¼ 8.3, 2.2 Hz, 1H),
7.82–7.75 (m, 3H), 7.69 (s, 2H), 7.15–7.08 (m, 2H), 4.61 (d,
J ¼ 5.5 Hz, 2H), 3.82 (s, 3H).13C NMR (125 MHz, DMSO) d 164.76,
159.69, 146.01, 141.64, 133.69 (d, J ¼ 14.6 Hz), 132.07, 130.62,
128.79, 122.11, 121.71, 115.35, 56.04, 35.50. HRMS (ESI) m/z:
[M þ H]þ calculated for C17H17ClN5O4S 422.0684, found 422.0690.
2.2.6.5.
4-Fluoro-N-((1–(3-fluorophenyl)-1H-1,2,3-triazol-4-
yl)methyl)-3-sulfamoylbenzamide (6q). White solid, yield: 76%,
m.p: 230–232 ꢀC; 1H NMR (500 MHz, DMSO) d 9.36 (t, J ¼ 5.5 Hz,
1H), 8.77 (s, 1H), 8.37 (dd, J ¼ 7.0, 2.2 Hz, 1H), 8.19 (ddd, J ¼ 8.5,
4.5, 2.3 Hz, 1H), 7.88–7.78 (m, 2H), 7.76 (s, 2H), 7.68–7.60 (m, 1H),
7.58–7.52 (m, 1H), 7.33 (td, J ¼ 8.4, 2.2 Hz, 1H), 4.62 (d, J ¼ 5.6 Hz,
2H).13C NMR (125 MHz, DMSO) d 164.65, 146.62, 138.38 (d,
J ¼ 10.7 Hz), 133.81 (d, J ¼ 9.4 Hz), 132.29 (d, J ¼ 9.3 Hz), 130.94
(d, J ¼ 3.4 Hz), 128.64, 121.88, 118.07–117.72 (m), 117.62 (d,
2.2.6. 4-Chloro-N-((1–(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-
3-sulfamoylbenzamide(6l)
White solid, yield: 83%, m.p: 189–190 ꢀC; 1H NMR (500 MHz,
DMSO) d 9.39 (t, J ¼ 5.6 Hz, 1H), 8.69 (s, 1H), 8.51 (d, J ¼ 2.2 Hz, J ¼ 22.1 Hz), 116.32 (d, J ¼ 3.0 Hz), 115.81, 115.64, 107.99, 107.78,