Journal of Medicinal Chemistry
Article
4-Chloro-N-isoquinolin-5-ylbenzenesulfonamide (6b). Yield 84%;
mp 205−207 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.58 (m, 3H),
7.66 (m, 3H), 7.99 (d, J = 6, 1H), 8.12 (d, J = 8.2, 1H), 8.51 (d, J = 6,
1H), 9.46 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ = 117.4 (CH),
127.7 (CH), 128.6 (CH), 128.9 (C), 129.0 (CH), 129.1 (CH), 129.8
(CH), 132.0 (C), 133.0 (C), 138.3 (C), 138.5 (C), 140.4 (CH), 151.6
(CH); HRMS (ES+) m/z [M + H] calcd for C15H12ClN2O2S
319.0308, found 319.0301. Anal. Calcd for C15H11ClN2O2S(H2O)0.3:
C, 55.57; H, 3.61; N, 8.64; S, 9.89. Found: C, 55.24; H, 3.48; N, 8.79;
S, 10.27.
N-Isoquinolin-5-ylbenzenesulfonamide (6c). Yield 40%; mp 198−
200 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.42 (m, 2H), 7.60 (m,
2H), 7.68 (m, 2H), 7.80 (dd, J = 3, J = 8.8, 2H), 7.97 (d, J = 8, 1H),
8.39 (d, J = 6, 1H), 9.26 (s, 1H), 10.44 (bs, 1H, NH); 13C NMR (75
MHz, DMSO-d6) δ = 116.0 (CH), 127.0 (CH), 127.6 (CH), 128.7
(CH), 129.2 (C), 129.6 (CH), 130.1 (CH), 131.9 (C), 133.3 (CH),
135.5 (C), 140.0 (C), 143.2 (CH), 152.8 (CH); HRMS (ES+) m/z [M
+ H] calcd for C15H13N2O2S 285.0698, found 285.0697.
4-Fluoro-N-quinoxalin-6-ylbenzenesulfonamide (7d). Yield 78%;
mp 186−190 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.41 (t, J = 8.8,
2H), 7.63 (dd, J = 2.3, J = 9, 1H), 7.70 (d, J = 2.3, 1H), 7.94 (dd, J =
5.1, J = 8.8, 2H), 8.01 (d, J = 9, 1H), 8.80 (d, J = 1.7, 1H), 8.84 (d, J =
1.7, 1H), 11.1 (bs, 1H, NH); 13C NMR (75 MHz, DMSO-d6) δ =
115.6 (CH), 117.1 (d, JC−F = 23.25, CH), 123.9 (CH), 130.2 (d, JC−F
= 9.75, CH), 130.8 (CH), 135.8 (C), 139.5 (C), 139.6 (C), 143.0 (C),
144.8 (CH), 146.6 (CH), 164.8 (d, JC−F = 251.25, C); HRMS (TOF+)
m/z [M + H] calcd for C14H11FN3O2S 304.0551, found 304.0661.
Anal. Calcd for C14H10FN3O2S: C, 55.44; H, 3.32; N, 13.85; S, 10.57.
Found: C, 55.58; H, 3.69; N, 13.96; S, 10.22.
N-Quinoxalin-6-yl-1-napthalenesulfonamide (7e). Yield 99%; mp
115−119 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.38 (m, 1H), 7.65
(m, 4H), 7.78 (td, J = 1.5, J = 7, 1H), 7.92 (d, J = 9, 1H), 8.06 (d, J =
8.3, 1H), 8.21 (d, J = 8.3, 1H), 8.40 (dd, J = 1.3, J = 7.5; 1H), 8.58 (bs,
1H, NH), 8.73 (d, J = 2, 1H), 8.78 (d, J = 2, 1H); 13C NMR (75 MHz,
DMSO-d6) δ = 114.1 (CH), 123.0 (CH), 124.3 (CH), 124.9 (CH),
127.5 (CH), 127.6 (C), 128.8 (CH), 129.6 (CH), 130.7 (CH), 134.0
(C), 134.1 (C), 135.3 (CH), 139.2 (C), 139.4 (C), 143.0 (C), 144.5
(CH), 146.5 (CH), 149.9 (CH); HRMS (ES+) m/z [M + H] calcd for
C18H14N3O2S 336.0807, found 336.0805.
4-Fluoro-N-isoquinolin-5-ylbenzenesulfonamide (6d). Yield 95%;
mp 233−237 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.35 (t, J = 8.7,
2H), 7.46 (d, J = 8, 1H), 7.61 (t, J = 8, 1H), 7.72 (dd, J = 5.2, J = 8.7,
2H), 7.80 (d, J = 6, 1H), 8.00 (d, J = 8, 1H), 8.43 (d, J = 6, 1H), 9.28
(s, 1H), 10.49 (bs, 1H, NH); 13C NMR (75 MHz, DMSO-d6) δ =
115.9 (CH), 116.8 (d, JC−F = 22.5, CH), 126.8 (CH), 127.6 (CH),
127.7 (CH), 129.2 (C), 130.1 (d, JC−F = 9.75, CH), 131.8 (C), 132.0
N-(2-Methyl-1H-indol-5-yl)-4-nitrobenzenesulfonamide (8a).
1
Yield 94%; mp 184−186 °C; H NMR (300 MHz, DMSO-d6): δ =
2.31 (s, 3H), 6.02 (s, 1H), 6.69 (dd, J = 2, J = 8.5, 1H), 7.08 (m, 2H),
7.88 (d, J = 9, 2H), 8.32 (d, J = 9, 2H), 10.08 (bs, 1H, NH), 10.91 (s,
1H, NH); 13C NMR (75 MHz, DMSO-d6): δ = 13.7 (CH3), 99.6
(CH), 111.1 (CH), 114.0 (CH), 116.7 (CH), 124.7 (CH), 128.0 (C),
128.7 (CH), 129.0 (C), 134.4 (C), 137.3 (C), 145.5 (C), 149.9 (C);
HRMS (EI+) m/z calcd for C15H13N3O4S: 331.0626, found 331.0623.
Anal. Calcd for C15H13N3O4S: C, 54.37; H, 3.95; N, 12.68; S, 9.68.
Found: C, 54.52; H, 4.21; N, 12.35; S, 9.47.
(C), 136.2 (d, JC−F = 3, C), 143.3 (CH), 152.8 (CH), 164.7 (d, JC−F
=
250.5, C); HRMS (TOF+) m/z [M + H] calcd for C15H12FN2O2S
303.0598, found 303.0605.
N-Isoquinolin-5-yl-1-naphthalenesulfonamide (6e). Yield 81%;
1
mp 196−200 °C; H NMR (300 MHz, DMSO-d6) δ = 7.43 (dd, J =
1.1, J = 7.5, 1H), 7.52 (m, 2H), 7.62 (m, 2H), 7.72 (d, J = 6.5, 1H),
7.90 (d, J = 8, 1H), 8.02 (d, J = 6.5, 1H), 8.04 (d, J = 8, 1H), 8.20 (d, J
= 8.3, 1H), 8.24 (dd, J = 1.1, J = 7.5, 1H), 8.78 (d, J = 8.3, 1H), 9.20 (s,
1H), 10.79 (bs, 1H, NH); 13C NMR (75 MHz, DMSO-d6) δ = 124.8
(CH), 126.3 (CH), 126.5 (CH), 127.3 (CH), 127.6 (CH), 128.0 (C),
128.4 (CH), 128.8 (CH), 129.4 (CH), 129.8 (CH), 129.9 (CH),
131.6 (C), 131.9 (C), 132.7 (C), 134.1 (C), 134.8 (CH), 134.9 (C),
143.0 (CH), 152.7 (CH); HRMS (ES+) m/z [M + H] calcd for
C19H15N2O2S:335.0854, found 335.0862. Anal. Calcd for
C19H14N2O2S: C, 68.24; H, 4.22; N, 8.38; S, 9.59. Found: C, 68.54;
H, 4.00; N, 8.72; S, 9.34.
4-Chloro-N-(2-methyl-1H-indol-5-yl)benzenesulfonamide (8b).
1
Yield 87%; mp 188−190 °C; H NMR (300 MHz, DMSO-d6) δ =
2.39 (s, 3H), 6.20 (s, 1H), 6.95 (dd, J = 2, J = 8.7, 1H), 7.06 (d, J = 2,
1H), 7.15 (d, J = 8.7, 1H), 7.55 (d, J = 8.8, 2H), 7.60 (d, J = 8.8, 2H),
9.8 (s, 1H, NH), 10.90 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6)
δ =13.7 (CH3), 99.5 (CH), 111.0 (CH), 113.7 (CH), 116.5 (CH),
128.6 (C), 129.0 (CH), 129.5 (CH), 134.3 (2C), 137.1 (C), 137.7
(C), 138.9 (C). HRMS (TOF+) m/z [M + H] calcd for C15H14
ClN2O2S 321.0459, found 321.0459. Anal. Calcd for C15H13ClN2O2S-
(H2O)0.4: C, 54.93; H, 4.24; N, 8.54; S, 9.78. Found: C, 54.70; H, 3.94;
N, 8.78; S, 9.51.
4-Nitro-N-quinoxalin-6-ylbenzenesulfonamide (7a). Yield 98%;
N-(2-Methyl-1H-indol-5-yl)benzenesulfonamide (8c). Yield 84%;
1
mp 251−254 °C; H NMR (300 MHz, DMSO-d6) δ = 7.64 (dd, J =
1
mp: 182−184 °C; H NMR (300 MHz, DMSO-d6) δ = 2.31 (s, 3H),
2.4, J = 9, 1H); 7.72 (d, J = 2.4, 1H); 8.01 (d, J = 9, 1H); 8.11 (d, J = 9,
2H); 8.37 (d, J = 9, 2H); 8.58 (bs, 1H, NH); 8.81 (d, J = 1.9, 1H);
8.85 (d, J = 1.9, 1H); 13C NMR (75 MHz, DMSO-d6) δ = 116.2
(CH), 124.0 (CH), 125.2 (CH), 128.7 (CH), 131.0 (CH), 138.9 (C),
139.8 (C), 143.0 (C), 144.8 (C), 145.1 (CH), 146.7 (CH), 150.4 (C);
HRMS (ES+) m/z [M + H] calcd for C14H11N4O4S 331.0501, found
331.0506. Anal. Calcd for C14H10N4O4S: C, 50.90; H, 3.05; N, 16.96;
S, 9.71. Found: C, 51.02; H, 3.31; N, 17.31; S, 9.53.
6.00 (s, 1H), 6.71 (dd, J = 2, J = 8.5, 1H), 7.06 (d, J = 8.5, 1H), 7.08 (s,
1H), 7.47 (m, 3H), 7.65 (d, J = 7.2, 2H), 9.72 (s, 1H, NH), 10.85 (s,
1H, NH); 13C NMR (75 MHz, DMSO-d6) δ = 13.7 (CH3), 99.5
(CH), 110.9 (CH), 113.4 (CH), 116.4 (CH), 124.3 (C), 127.0 (CH),
128.9 (C), 129.3 (CH), 132.7 (CH), 134.2 (C), 137.0 (C), 140.1 (C);
HRMS (ES+) m/z [M + H] calcd for C15H15N2O2S 287.0854, found
287.0844. Anal. Calcd for C15H14N2O2S: C, 61.94; H, 5.02; N, 9.63; S,
11.02. Found: C, 62.22; H, 4.89; N, 9.23; S, 10.66.
4-Chloro-N-quinoxalin-6-ylbenzenesulfonamide (7b). Yield 99%;
mp 190−192 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.66 (m, 4H),
7.85 (d, J = 9, 2H), 8.01 (d, J = 9, 1H), 8.81 (s, 1H), 8.84 (s, 1H), 11.2
(bs, 1H, NH); 13C NMR (75 MHz, DMSO-d6) δ = 115.7 (CH), 123.9
(CH), 129.0 (CH), 130.1 (CH), 130.9 (CH), 138.3 (C), 138.6 (C),
139.4 (C), 139.0 (C), 143.0 (C), 144.9 (CH), 146.6 (CH); HRMS
(ES+) m/z [M + H] calcd for C14H11ClN3O2S 320.0261, found
320.0264. Anal. Calcd for C14H10ClN3O2S: C, 52.58; H, 3.15; N,
13.14; S, 10.03. Found: C, 52.63; H, 3.27; N, 13.10; S, 10.04.
N-Quinoxalin-6-ylbenzenesulfonamide (7c). Yield 46%; mp 195−
200 °C; 1H NMR (300 MHz, DMSO-d6) δ = 7.57 (m, 3H), 7.62 (dd,
J = 2.4, J = 9, 1H), 7.68 (d, J = 2.4, 1H), 7.87 (dd, J = 1.7, J = 7.5, 2H),
7.94 (d, J = 9, 1H), 8.6 (bs, 1H, NH); 8.78 (d, J = 1.8, 1H), 8.83 (d, J
= 1.8, 1H); 13C NMR (75 MHz, DMSO-d6) δ = 115.3 (CH), 123.8
(CH), 127.1 (CH), 129.9 (CH), 130.7 (CH), 133.7 (CH), 139.5 (C),
139.7 (C), 143.0 (C), 144.7 (CH), 146.6 (CH), 150.0 (C); HRMS
(ES+) m/z [M + H] calcd for C14H12N3O2S 286.0650, found
286.0647.
4-Fluoro-N-(2-methyl-1H-indol-5-yl)benzenesulfonamide (8d).
Yield 92%; mp 155−157 °C; H NMR (300 MHz, DMSO-d6) δ =
1
2.50 (s, 3H), 6.01 (s, 1H), 6.67 (dd, J = 2, J = 8.7, 1H), 7.06 (d, J = 2,
1H), 7.09 (d, J = 8.7, 1H), 7.33 (t, J = 8.8, 2H), 7.68 (dd, J = 5.1, J =
8.8, 2H), 9.74 (s, 1H, NH), 10.86 (s, 1H, NH); 13C NMR (75 MHz,
DMSO-d6) δ = 13.7 (CH3), 99.5 (CH), 111.0 (CH), 113.7 (CH),
116.3 (CH), 116.6 (CH), 124.5 (C), 128.7 (C), 130.1 (CH), 134.3
(C), 136.3 (C), 137.1 (C), 162 (d, JC−F = 260, C); HRMS (ES+) m/z
[M + H] calcd for C15H14FN2O2S 305.0760, found 305.0766. Anal.
Calcd for C15H13FN2O2S(H2O)0.3: C, 58.16; H, 4.42; N, 9.04; S,
10.35. Found: C, 58.10; H, 4.34; N, 9.16; S, 10.22.
2-Methyl-1H-indol-5-yl-1-naphthalenesulfonamide (8e). Yield
1
44%; mp 198−190 °C; H NMR (300 MHz, DMSO-d6) δ = 2.27
(s, 3H), 5.92 (s, 1H), 6.59 (dd, J = 2, J = 8.7, 1H), 6.99 (m, 2H), 7.50
(t, J = 8.1, 1H), 7.66 (td, J = 1.3, J = 7, 1H), 7.71 (td, J = 1.5, J = 7,
1H), 8.04 (m, 2H), 8.13 (d, J = 8.1, 1H), 8.80 (d, J = 8.7, 1H), 10.10
(s, 1H, NH), 10.78 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6) δ =
13.7 (CH3), 99.4 (CH), 110.9 (CH), 112.8 (CH), 115.9 (CH), 124.7
8992
dx.doi.org/10.1021/jm4006127 | J. Med. Chem. 2013, 56, 8984−8998