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Medicinal Chemistry Research (2021) 30:473–482
127.32, 124.75, 114.17, 79.82, 75.07, 70.27, 54.85, 49.15,
34.86, 32.36, 30.29, 22.33, 19.21, 16.84, 10.86. HRMS
(AP-ESI) m/z: calcd for C26H34ClN3O4S [M+H]+
520.2037; found, 520.2040.
(S)-2-amino-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-
(prop-2-yn-1-yl)sulfamoyl)phenethyl)-2-(thiophen-3-yl)
acetamide (10)
1H NMR (400 MHz, DMSO-d6) δ 7.99 (s, 1H),
7.70–7.39 (m, 3H), 7.38-7.08 (m, 3H), 7.08-6.67 (m, 3H),
5.08 (d, J = 72.0 Hz, 1H), 4.57–4.03 (m, 2H), 3.85 (m, 2H),
3.52 (d, J = 43.1 Hz, 3H), 2.95 (s, 1H), 2.86–2.56 (m, 1H),
1.61 (m, 2H), 0.87 (m, 3H). 13C NMR (101 MHz, DMSO) δ
171.79, 155.48, 143.63, 139.00, 129.90, 129.73, 128.73,
128.16, 127.77, 127.48, 127.30, 127.25, 127.12, 124.40,
113.67, 79.80, 75.03, 70.06, 50.93, 48.77, 44.26, 34.53,
32.37, 22.43, 10.92. HRMS (AP-ESI) m/z: calcd for
C27H30ClN3O4S2 [M+H]+ 560.1425; found, 560.1427.
(R)-2-amino-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-
(prop-2-yn-1-yl)sulfamoyl)phenethyl)-2-(thiophen-3-yl)
acetamide (11)
(S)-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-(prop-2-yn-
1-yl)sulfamoyl)phenethyl)pyrrolidine-2-carboxamide (6)
1H NMR (400 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.64 (M,
2H), 7.40 (d, J = 7.8 Hz, 1H), 7.34–6.85 (m, 4H),
4.55–4.15 (m, 2H), 3.88 (m, 2H), 3.56 (d, J = 18.7 Hz, 2H),
3.10–2.67 (m, 6H), 1.83–1.46 (m, 4H), 1.05 (t, J = 7.2 Hz,
4H), 0.89 (dt, J = 10.6, 7.3 Hz, 3H). 13C NMR (101 MHz,
DMSO) δ 172.38, 155.82, 143.64, 139.31, 129.97, 129.80,
128.50, 128.43, 127.32, 124.40, 114.04, 79.81, 75.08,
70.12, 58.27, 58.04, 46.57, 46.08, 32.35, 29.92, 29.76,
22.31, 10.82, 9.83. HRMS (AP-ESI) m/z: calcd for
C26H32ClN3O4S [M+H]+ 518.1880; found, 518.1875.
(R)-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-(prop-2-yn-
1-yl)sulfamoyl)phenethyl)pyrrolidine-2-carboxamide (7)
1H NMR (400 MHz, DMSO-d6) δ 8.10 (q, J = 5.9 Hz,
1H), 7.79–7.60 (m, 2H), 7.56–7.42 (m, 1H), 7.42–6.93 (m,
4H), 4.69–4.39 (m, 2H), 4.03-3.93 (m, 2H), 3.72-3.58 (m,
2H), 3.28-2.57 (m, 6H), 2.08-1.51 (m, 4H), 1.46-1.16 (m,
4H), 0.96 (M, 3H). 13C NMR (101 MHz, DMSO) δ 169.01,
158.62, 144.07, 139.14, 129.97, 128.76, 127.32, 127.27,
126.27, 119.50, 113.91, 78.89, 75.07, 70.14, 58.34, 58.18,
47.25, 46.06, 32.36, 29.57, 24.00, 22.29, 10.93, 9.02.
HRMS (AP-ESI) m/z: calcd for C26H32ClN3O4S [M+H]+
518.1880; found, 518.1875.
(R)-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-(prop-2-yn-
1-yl)sulfamoyl)phenethyl)thiazolidine-2-carboxamide (8)
1H NMR (400 MHz, DMSO-d6) δ 8.01 (m, 1H), 7.76-
7.54 (m, 2H), 7.49-7.06 (m, 3H), 7.06–6.77 (m, 2H),
4.60–4.20 (m, 2H), 4.03–3.77 (m, 2H), 3.64-3.55 (m, 2H),
3.15–2.50 (m, 6H), 1.65 (m, 2H), 1.30-0.78 (m, 6H). 13C
NMR (101 MHz, DMSO) δ 177.13, 155.82, 138.98,
138.69, 130.06, 130.03, 129.77, 128.33, 127.28, 124.55,
113.80, 79.82, 75.07, 70.09, 61.20, 56.79, 48.73, 32.37,
29.49, 29.15, 22.48, 10.95, 10.92. HRMS (AP-ESI) m/z:
calcd for C25H30ClN3O4S2 [M+Na]+ 558.1264; found,
558.1260.
1H NMR (400 MHz, DMSO-d6) δ 8.07 (s, 1H),
7.79–7.46 (m, 3H), 7.46–7.18 (m, 3H), 7.17–6.93 (m, 2H),
6.86 (d, J = 10.6 Hz, 1H), 5.33–4.87 (m, 1H), 4.67-4.08 (m,
2H), 3.94 (m, 2H), 3.60 (d, J = 43.7 Hz, 3H), 3.03 (s, 1H),
2.94–2.66 (m, 1H), 1.69 (m, 2H), 0.94 (m, 3H). 13C NMR
(101 MHz, DMSO) δ 171.77, 155.50, 143.65, 139.02,
129.90, 129.74, 128.74, 128.18, 127.93, 127.50, 127.32,
127.26, 127.13, 124.42, 113.70, 79.82, 75.04, 70.07, 51.10,
48.78, 44.25, 34.53, 32.37, 22.44, 10.92. HRMS (AP-ESI)
m/z: calcd for C27H30ClN3O4S2 [M+H]+ 560.1445; found,
560.1446.
(S)-2-amino-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-
(prop-2-yn-1-yl)sulfamoyl)phenethyl)-3-(thiophen-2-yl)
propanamide (12)
1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.76 (d,
J = 7.8 Hz, 2H), 7.45–7.22 (m, 4H), 7.09–6.93 (m, 3H),
6.86 (d, J = 21.7 Hz, 1H), 4.45 (d, J = 35.0 Hz, 2H), 3.94
(m, 3H), 3.82–3.50 (m, 4H), 3.21–3.02 (m, 2H), 3.01–2.65
(m, 3H), 1.77 (m, 2H), 1.01 (m, 3H). 13C NMR (101 MHz,
DMSO) δ 174.92, 155.52, 143.93, 138.96, 129.82, 129.75,
128.27, 128.07, 127.96, 127.32, 127.11, 126.48, 124.80,
124.47, 113.60, 79.83, 75.00, 70.03, 55.36, 53.29, 48.83,
43.84, 36.51, 32.36, 22.47, 10.94. HRMS (AP-ESI) m/z:
calcd for C28H32ClN3O4S2 [M+H]+ 596.1420; found,
596.1417.
(R)-2-amino-N-(5-chloro-2-propoxybenzyl)-3-phenyl-N-
(4-(N-(prop-2-yn-1-yl)sulfamoyl)phenethyl)propanamide
(9)
(S)-2-amino-N-(5-chloro-2-propoxybenzyl)-N-(4-(N-
(prop-2-yn-1-yl)sulfamoyl)phenethyl)-3-(thiophen-3-yl)
propanamide (13)
1H NMR (400 MHz, DMSO-d6) δ 7.76 (dd, J = 8.3, 3.1
Hz, 2H), 7.29 (m, 8H), 7.10–6.93 (m, 2H), 4.42–4.27 (m,
2H), 3.98 (q, J = 6.0 Hz, 2H), 3.77–3.45 (m, 3H), 3.08 (m,
1H), 2.94–2.62 (m, 4H), 2.09–1.62 (m, 4H), 1.01 (m, 3H).
13C NMR (101 MHz, DMSO) δ 175.39, 155.53, 143.96,
138.92, 129.79, 129.73, 129.63, 128.57, 128.31, 128.09,
127.29, 126.63, 124.65, 124.40, 113.77, 79.82, 75.01,
70.00, 53.13, 48.62, 43.69, 42.75, 35.07, 32.36, 22.46,
10.95. HRMS (AP-ESI) m/z: calcd for C30H34ClN3O4S [M
+H]+ 568.2037; found, 568.2039.
1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 15.2 Hz,
1H), 7.76 (dd, J = 8.3, 3.2 Hz, 2H), 7.52-7.22 (m, 4H), 7.18
(dd, J = 8.9, 2.4 Hz, 1H), 7.12–6.85 (m, 3H), 4.40 (d, J =
4.2 Hz, 2H), 3.99 (t, J = 6.4 Hz, 2H), 3.86 (t, J = 6.9 Hz,
1H), 3.75–3.45 (m, 4H), 3.15–3.01 (m, 1H), 2.99–2.63 (m,
4H), 1.85–1.65 (m, 2H), 1.01 (m, 3H). 13C NMR (101
MHz, DMSO) δ 175.39, 155.52, 143.99, 139.27, 129.87,
129.74, 129.48, 128.33, 128.09, 127.29, 127.27, 126.10,
124.43, 122.50, 113.61, 79.82, 75.03, 70.01, 52.55, 52.36,