274
X.-y. Li et al. / European Journal of Medicinal Chemistry 154 (2018) 267e279
146.86, 141.23, 130.28, 129.31, 128.76, 126.89, 122.36, 118.24, 111.54,
17.79. ESI-HRMS m/z calcd for C18H17N5O5NaS. [M þ Na]þ 438.0827,
found: 438.0827.
111.69,110.13. ESI-HRMS calcd for C17H15N5O5NaS. [M þ Na]þ
424.0692, found: 424.0705.
4.1.3.9. N'-(2-benzyl)-3-(2,4-dihydroxypyrimidine-5-sulfonamido)
4.1.3.3. N'-(3-benzyl)-4-(2,4-dihydroxypyrimidine-5-sulfonamido)
benzoyl hydrazide (6b). An off yellow solid, yield: 62.34%. Mp:
benzoyl hydrazide (5c). A light yellow solid, yield: 71.33%. Mp:
135e139 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 11.60 (br. s., 1 H), 10.36
173e174 ꢀC.1H NMR (600 MHz, DMSO-d6)
d
11.80 (br. s., 1 H), 11.62
(s, 2 H), 8.10 (s,1 H), 7.62 (d, J ¼ 1.88 Hz,1 H), 7.38e7.41 (m,1 H), 7.30
(d, J ¼ 10.35 Hz, 1 H), 7.25 (d, J ¼ 2.82 Hz, 1 H), 6.98e7.05 (m, 2 H),
6.63e6.71 (m, 2 H),2.20 (s, 3 H); 13C NMR (150 MHz, DMSO-d6)
(s, 1 H), 10.44 (s, 1 H), 10.39 (d, J ¼ 4.52 Hz, 2 H), 8.11 (s, 1 H), 7.95 (s,
1 H), 7.82 (d, J ¼ 8.09 Hz, 2 H), 7.64 (d, J ¼ 1.69 Hz, 1 H), 7.59 (d,
J ¼ 7.91 Hz, 1 H), 7.41 (t, J ¼ 7.91 Hz, 1 H), 7.33 (d, J ¼ 7.72 Hz,
d
170.83, 166.44, 159.08, 151.01, 149.09, 147.24, 138.49, 134.59,
2 H),2.38 (s, 3 H); 13C NMR (150 MHz, DMSO-d6)
d
166.70, 155.35,
130.46, 129.69, 126.92, 122.78, 122.40, 119.22, 119.08, 111.46, 111.17,
17.78. ESI-HRMS calcd for C18H17N5O5NaS. [M þ Na]þ 438.0848,
found: 438.0855.
152.53, 150.40, 138.22, 129.35, 129.05, 128.76, 123.48, 119.82, 119.74,
113.33, 113.11, 111.97, 110.14, 21.79. ESI-HRMS m/z calcd for
C
18H17N5O5NaS. [M þ Na]þ 424.0692, found: 438.0869.
4.1.3.10. N'-(3-benzyl)-3-(2,4-dihydroxypyrimidine-5-sulfonamido)
4.1.3.4. N'-(2-chlorophenyl)-4-(2,4-dihydroxypyrimidine-5-
benzoyl hydrazide (6c). A yellow solid, yield: 73.80%. Mp:
sulfonamido)benzoyl hydrazide (5d). A white solid, yield: 63.00%.
158e160 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 11.53 (br. s., 1 H), 10.47
Mp: 163e167 ꢀC.1H NMR (600 MHz, DMSO-d6)
d
11.50 (br. s., 1 H),
(s, 1 H), 10.41 (s, 1 H), 8.11 (s, 1 H), 7.74 (s, 1 H), 7.71 (d, J ¼ 5.84 Hz,
1 H), 7.64 (s, 1 H), 7.59 (d, J ¼ 7.72 Hz, 1 H), 7.38e7.43 (m, 3 H), 7.32
(d, J ¼ 8.09 Hz, 1 H),2.38 (s, 3 H); 13C NMR (150 MHz, DMSO-d6)
10.38 (s, 1 H), 8.22 (s, 1 H), 8.22 (s, 1 H), 7.82e7.84 (m, 2 H),
7.82e7.84 (m, 2 H), 7.30 (d, J ¼ 7.91 Hz,1 H), 7.21 (d, J ¼ 8.85 Hz, 2 H),
7.12e7.15 (m, 1 H), 6.81 (d, J ¼ 8.09 Hz, 1 H),6.75 (t, J ¼ 6.87 Hz, 1 H);
d
167.57, 152.75, 150.18, 149.30, 138.23, 134.42, 129.31, 129.06,
13C NMR (150 MHz, DMSO-d6)
d
166.27, 159.47, 152.54, 151.48,
119.85, 118.12, 117.24, 116.25, 114.68, 113.30, 113.27, 112.46,
110.08,21.80. ESI-HRMS calcd for C18H17N5O5NaS. [M þ Na]þ
438.0848, found: 438.0841.
145.36, 141.79, 129.59, 129.06, 128.27, 127.36, 120.07, 118.16, 117.07,
113.60,110.14. ESI-HRMS calcd for C17H14ClN5O5NaS. [M þ Na]þ
458.0302, found: 458.0244.
4.1.3.11. N'-(2-chlorophenyl)-3-(2,4-dihydroxypyrimidine-5-
4.1.3.5. N'-(3-chlorophenyl)-4-(2,4-dihydroxypyrimidine-5-
sulfonamido)benzoyl hydrazide (6d). A white powder, yield: 71.33%.
sulfonamido) benzoyl hydrazide (5e). A white solid, yield: 76.50%.
Mp: 168e170 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 10.60 (br. s., 1 H),
Mp: 187e190 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d
10.61e11.30 (m,
1 H), 10.23 (s, 1 H), 8.18 (s, 1 H), 7.78 (d, J ¼ 8.66 Hz, 2 H), 7.11e7.19
(m, 3 H), 6.67e6.73 (m, 3 H);13
NMR (150 MHz, DMSO-d6)
166.26, 159.00, 151.66, 150.90, 149.35, 141.38,
10.37 (br. s., 1 H), 10.37 (br. s., 1 H), 8.11 (s, 1 H), 7.65 (s, 1 H), 7.59 (d,
J ¼ 7.15 Hz, 1 H), 7.54e7.57 (m, 2 H), 7.52 (t, J ¼ 7.53 Hz, 1 H),
7.45e7.49 (m, 1 H), 7.39 (t, J ¼ 7.81 Hz, 1 H),7.31 (d, J ¼ 8.09 Hz, 1 H);
C
d
13C NMR (150 MHz, DMSO-d6)
d 165.34, 157.98, 149.66, 147.72,
133.92,130.90,129.04,127.63,118.45,118.20, 111.97, 111.36,111.09. ESI-
HRMS calcd for C17H14ClN5O5NaS. [M þ Na] þ 458.0302, found:
458.0306.
144.17, 137.37, 133.11, 128.61, 128.54, 127.21, 121.96, 121.60, 118.99,
118.24, 116.69, 112.40,110.09. ESI-HRMS calcd for C17H14ClN5O5NaS.
[M þ Na]þ 458.0302, found: 458.0298.
4.1.3.6. N'-(2-fluorophenyl)-4-(2,4-dihydroxypyrimidine-5-
sulfonamido) benzoyl hydrazide (5f). A yellow solid, yield: 80.20%.
4.1.3.12. N'-(3-chlorophenyl)-3-(2,4-dihydroxypyrimidine-5-
sulfonamido)benzoyl hydrazide (6e). An off white powder, yield:
Mp: 141e144 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d
11.91 (br. s., 1 H),
70.43%. Mp: 170e173 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 10.41 (br.
11.63 (s, 1 H), 10.61 (br. s., 1 H), 10.30 (s, 1 H), 8.23 (s, 1 H), 7.82 (d,
J ¼ 8.62 Hz, 2 H), 7.20 (d, J ¼ 8.80 Hz, 2 H), 7.08 (dd, J ¼ 11.65,
7.79 Hz, 1 H), 6.97 (t, J ¼ 7.61 Hz, 1 H), 6.80 (t, J ¼ 8.53 Hz, 1 H),
s., 1 H), 8.23 (s, 1 H), 8.10 (s, 1 H), 7.61 (s, 1 H), 7.57 (d, J ¼ 7.52 Hz,
1 H), 7.35e7.39 (m, 1 H), 7.30 (d, J ¼ 7.70 Hz, 1 H), 7.17 (t, J ¼ 7.89 Hz,
1 H),6.70e6.77 (m, 3 H); 13C NMR (150 MHz, DMSO-d6)
d 166.55,
6.70e6.74 (m, 1 H); 13C NMR (150 MHz, DMSO-d6)
d
166.26, 159.00,
159.05, 151.51, 150.93, 149.01, 138.52, 134.25, 133.95, 130.96, 129.75,
122.85, 122.49, 119.09, 118.55, 112.00, 111.33,111.21. ESI-HRMS calcd
for C17H14ClN5O5NaS. [M þ Na]þ 458.0302, found: 458.0281.
151.50, 150.86, 149.92, 149.32, 141.33, 137.58, 137.50, 129.04, 127.75,
125.03, 118.22, 114.18, 113.14,111.08. ESI-HRMS calcd for
C
17H14FN5O5NaS. [M þ Na]þ 442.0597, found: 442.0574.
4.1.3.13. N'-(2-fluorophenyl)-3-(2,4-dihydroxypyrimidine-5-
sulfonamido)benzoyl hydrazide (6f). A yellow solid, yield: 60.86%.
4.1.3.7. N'-(4-fluorophenyl)-4-(2,4-dihydroxypyrimidine-5-
sulfonamido) benzoyl hydrazide (5g). A yellow solid, yield: 82.00%.
Mp: 162e164 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 11.62 (br. s., 1 H),
Mp: 177e179 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d
11.86 (br. s., 1 H),
10.41 (d, J ¼ 2.20 Hz, 1 H), 8.12 (s, 1 H), 7.81 (s, 1 H), 7.57e7.65 (m,
2 H), 7.40 (t, J ¼ 8.16 Hz, 1 H), 7.26e7.34 (m, 1 H), 7.10 (dd, J ¼ 12.01,
8.16, 1.10 Hz, 1 H), 7.00 (t, J ¼ 7.61 Hz, 1 H), 6.77e6.86 (m,
11.62 (s, 1 H), 10.59 (s, 1 H), 10.25 (s, 1 H), 8.23 (s, 1 H), 7.81 (d,
J ¼ 8.66 Hz, 2 H), 7.28 (d, J ¼ 8.85 Hz, 2 H), 7.20 (d, J ¼ 8.66 Hz,
2 H),6.69e6.76 (m, 2 H); 13C NMR (150 MHz, DMSO-d6)
d
165.82,
1 H),6.70e6.77 (m, 1 H); 13C NMR (150 MHz, DMSO-d6)
d 166.54,
165.28, 165.28, 159.02, 150.96, 149.48, 141.48, 130.65, 129.15, 127.44,
118.20, 116.08, 115.93,111.02. ESI-HRMS calcd for C17H14FN5O5NaS.
[M þ Na]þ 442.0597, found: 442.0611.
159.04, 151.51, 150.89, 149.93, 148.96, 138.48, 134.33,129.70,125.06,
122.89,122.52,119.11,115.43,115.31,114.11,111.20. ESI-HRMS calcd
for C17H14FN5O5NaS. [M þ Na]þ 442.0597, found: 442.0607.
4.1.3.8. N0-phenyl-3-(2,4-dihydroxypyrimidine-5-sulfonamido)ben-
4.1.3.14. N'-(4-fluorophenyl)-3-(2,4-dihydroxypyrimidine-5-
sulfonamido)benzoyl hydrazide (6g). A yellow solid, yield: 80.50%.
zoyl hydrazide (6a). A yellow solid, yield: 79.00%. Mp: 132e137 ꢀC.
1H NMR (600 MHz, DMSO-d6)
d
11.60 (br. s., 1 H), 10.32 (d,
Mp: 165e169 ꢀC. 1H NMR (600 MHz, DMSO-d6)
d 11.79 (br. s., 1 H),
J ¼ 2.82 Hz, 1 H), 8.10 (s, 1 H), 7.86 (d, J ¼ 3.01 Hz, 1 H), 7.61 (d,
J ¼ 1.51 Hz, 1 H), 7.34e7.39 (m, 1 H), 7.29 (d, J ¼ 7.91 Hz, 1 H),
7.11e7.20 (m, 2 H), 6.76 (d, J ¼ 7.72 Hz, 2 H),6.71 (t, J ¼ 7.25 Hz, 1 H);
11.61 (s, 1 H), 10.35 (s, 2 H), 8.10 (s, 1 H), 7.86 (d, J ¼ 3.01 Hz, 1 H),
7.60 (d, J ¼ 1.88 Hz, 1 H), 7.39 (t, J ¼ 8.19 Hz, 1 H), 7.30 (d, J ¼ 7.15 Hz,
1 H), 6.94e7.03 (m, 2 H),6.72e6.82 (m, 2 H); 13C NMR (150 MHz,
13C NMR (150 MHz, DMSO-d6)
d
169.76, 165.47, 157.99, 149.87,
DMSO-d6)
d 166.55, 159.03, 150.88, 148.93, 138.45, 134.47, 129.68,
148.83, 147.94, 137.39, 133.50, 128.60, 128.16, 121.70, 121.42, 118.06,
122.82, 122.49, 119.08, 115.75, 115.60, 113.99, 113.94,111.24. ESI-