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A. You et al. / European Journal of Medicinal Chemistry 93 (2015) 255e262
172.1, 147.5, 140.3, 131.9, 127.2, 118.3, 29.5, 13.7, 9.5. ESI-MS m/
z ¼ 265.2 [M þ 1]þ.
4 . 2 . 2 . 1 2 . 1 - ( 4 - ( 4 - F l o r o b e n z a m i d o p h e n y l ) ) e t h y l -
idenethiosemicarbazide (7l). Solid product, yield 87%, m.p.
201e202 ꢀC. 1H NMR (300 MHz, DMSO-d6)
d: 10.34 (s, 1H), 10.15 (s,
1H), 8.24 (s, 1H), 8.10e7.97 (m, 2H), 7.93 (d, J ¼ 8.6 Hz, 3H), 7.79 (d,
4.2.2.5. 1-(4-Butyramidophenyl)ethylidenethiosemicarbazide
Yellowish solid product, yield 82%, m.p. 217e218 ꢀC. 1H NMR
(300 MHz, DMSO-d6) : 10.16 (s, 1H), 10.00 (s, 1H), 8.25 (s, 1H), 7.88
(7e).
J ¼ 8.2 Hz, 2H), 7.36 (t, J ¼ 8.4 Hz, 2H), 2.29 (s, 3H). 13C NMR
(75 MHz, DMSO-d6) d: 179.2, 165.0, 148.0, 140.6, 133.2, 131.0, 130.9,
d
127.6, 120.1, 115.9, 115.7, 14.2. ESI-MS m/z ¼ 331.4 [M þ 1]þ.
(d, J ¼ 8.8 Hz, 3H), 7.62 (d, J ¼ 8.9 Hz, 2H), 2.30 (t, J ¼ 7.4 Hz, 2H),
2.26 (s, 3H), 1.69e1.54 (m, 2H), 0.92 (t, J ¼ 7.4 Hz, 3H). 13C NMR
4 . 2 . 2 . 1 3 . 4 - ( 4 - M e t h o x y b e n z a m i d o p h e n y l ) e t h y l -
idenethiosemicarbazide (7m). Solid product, yield 85%, m.p.
(75 MHz, DMSO-d6) d: 178.6, 171.3, 147.5, 140.3, 132.0, 127.11, 118.3,
18.4, 13.7,13.6. ESI-MS m/z ¼ 279.2 [M þ 1]þ.
202e203 ꢀC. 1H NMR (300 MHz, DMSO-d6)
d
: 10.15 (d, J ¼ 7.7 Hz,
2H), 8.23 (s, 1H), 7.93 (t, J ¼ 8.7 Hz, 5H), 7.79 (d, J ¼ 7.9 Hz, 2H), 7.05
4.2.2.6. 1-(4-iso-Butyramidophenyl)ethylidenethiosemicarbazide
(d, J ¼ 7.4 Hz, 3H), 3.83 (s, 3H), 2.53 (s, 1H), 2.28 (s, 3H). 13C NMR
(7f). Solid product, yield 88%, m.p. 216e217 ꢀC. 1H NMR (300 MHz,
(75 MHz, DMSO-d6) d:178.7, 164.9, 162.9, 147.5, 140.4, 132.4, 129.8,
DMSO-d6)
d: 10.16 (s, 1H), 9.96 (s, 1H), 8.25 (s, 1H), 7.89 (d,
127.0, 126.5, 119.5, 113.6, 55.4, 13.7. ESI-MS (m/z) ¼ 343.4 [M þ 1]þ.
J ¼ 8.8 Hz, 3H), 7.63 (d, J ¼ 8.8 Hz, 2H), 2.60 (m, 1H), 2.26 (s, 3H), 1.10
(d, J ¼ 6.8 Hz, 6H). 13C NMR (75 MHz, DMSO-d6)
d: 178.6, 175.3,
4.2.2.14. 1-(4-Phenylacetamidophenyl)ethylidenethiosemicarbazide
147.5140.4, 131.9, 127.1, 118.4, 35.0, 19.5, 13.7. Anal. Calcd for
(7n). Solid product, yield 84%, m.p. 211e212 ꢀC. 1H NMR (300 MHz,
C
13H18N4OS: C, 56.09; H, 6.52; N, 20.13; found: C, 56.04; H, 6.40; N,
20.41. ESI-MS m/z ¼ 279.2 [M þ 1]þ.
DMSO-d6)
d: 10.32 (s, 1H), 10.17 (s, 1H), 8.25 (s, 1H), 7.90 (d,
J ¼ 8.8 Hz, 3H), 7.62 (d, J ¼ 8.8 Hz, 2H), 7.34 (d, J ¼ 4.4 Hz, 4H),
7.29e7.23 (m, 1H), 3.66 (s, 2H), 2.26 (s, 3H). 13C NMR (75 MHz,
4.2.2.7. 1-(4-Pentanamidophenyl)ethylidenethiosemicarbazide (7g).
Yellowish solid product, yield 87%, m.p. 213e214 ꢀC. 1H NMR
(300 MHz, DMSO-d6) d: 10.18 (s, 1H), 10.01 (s, 1H), 8.27 (s, 1H), 7.89
DMSO-d6) d: 178.61, 169.2, 147.5, 140.1, 135.8, 132.2, 129.1, 128.3,
127.2, 126.5, 118.4, 43.3, 13.7. ESI-MS m/z ¼ 327.3 [M þ 1]þ.
(d, J ¼ 8.8 Hz, 3H), 7.62 (d, J ¼ 8.8 Hz, 2H), 2.33 (t, J ¼ 7.4 Hz, 2H),
4.2.2.15. 1-(3-Acetamidophenyl)ethylidenethiosemicarbazide (8a).
Brown powder product, yield 88%, m.p. 204e205 ꢀC. 1H NMR
(300 MHz, DMSO-d6) d: 10.35 (s, 1H), 9.99 (s, 1H), 8.41 (s, 1H), 7.95
2.27 (s, 3H), 1.65e1.52 (m, 2H), 1.40e1.25 (m, 2H), 0.90 (t, J ¼ 7.3 Hz,
3H). 13C NMR (75 MHz, DMSO-d6)
d: 178.6, 171.4, 147.5, 140.3, 132.0,
127.1, 118.3, 36.1, 27.1, 21.8, 13.7, 13.7. Anal. Calcd for C14H20N4OS: C,
57.51; H, 6.89; N, 19.16; found: C, 57.25; H, 6.77; N, 19.52. ESI-MS m/
z ¼ 293.3 [M þ 1]þ.
(s, 1H), 7.78 (s, 1H), 7.73 (d, J ¼ 8.0 Hz, 1H), 7.63 (d, J ¼ 8.0 Hz, 1H),
7.33 (t, J ¼ 8.0 Hz, 1H), 2.31 (s, 3H), 2.08 (s, 3H). 13C NMR (75 MHz,
DMSO-d6) d: 178.9,168.4, 147.7, 139.2, 138.1,128.6,121.3, 120.0,117.1,
24.0, 14.1. ESI-MS m/z ¼ 251.2 [M þ 1]þ.
4.2.2.8. 1-(4-Hexanamidophenyl)ethylidenethiosemicarbazide (7h).
Yellowish solid product, yield 81%, m.p. 178e179 ꢀC. 1H NMR
(300 MHz, DMSO-d6) d: 10.17 (s, 1H), 10.00 (s, 1H), 8.26 (s, 1H), 7.88
4.2.2.16. 1-(3-Trifloroacetamidophenyl)ethylidenethiosemicarbazide
(8b). Solid product, yield 93%, m.p.168 ꢀC (dec.). 1H NMR (300 MHz,
(d, J ¼ 8.8 Hz, 3H), 7.62 (d, J ¼ 8.8 Hz, 2H), 2.31 (t, J ¼ 7.4 Hz, 2H),
DMSO-d6)
(d, J ¼ 8.0 Hz, 2H), 7.75 (d, J ¼ 8.0 Hz,1H), 7.44 (t, J ¼ 8.0 Hz,1H), 2.31
(s, 3H). 13C NMR (75 MHz, DMSO-d6)
: 179.0, 154.8, 154.3, 146.9,
d: 11.27 (s, 1H), 10.38 (s, 1H), 8.43 (s, 1H), 8.07 (s, 1H), 7.82
2.26 (s, 3H), 1.66e1.53 (m, 2H), 1.36e1.23 (m, 4H), 0.88 (t, J ¼ 6.9 Hz,
3H). 13C NMR (75 MHz, DMSO-d6)
d: 178.6, 171.4, 147.5, 140.3, 132.0,
d
127.1, 118.3, 36.4, 30.9, 24.7, 21.9, 13.8, 13.7. ESI-MS m/z ¼ 307.3
138.5, 136.2, 128.9, 123.9, 121.8, 119.3, 14.0. ESI-MS m/z ¼ 305.2
[M þ 1]þ.
[M þ 1]þ.
4.2.2.9. 1-(4-Heptanamidophenyl)ethylidenethiosemicarbazide (7i).
Solid product, yield 83%, m.p. 187e188 ꢀC. 1H NMR (300 MHz,
4.2.2.17. 1-(3-iso-Butyramidophenyl)ethylidenethiosemicarbazide
(8c). Solid product, yield 85%, m.p. 198e199 ꢀC. 1H NMR (300 MHz,
DMSO-d6)
d: 10.16 (s, 1H), 10.00 (s, 1H), 8.25 (s, 1H), 7.88 (d,
DMSO-d6) d: 10.34 (s, 1H), 9.86 (s, 1H), 8.41 (s, 1H), 7.99 (s, 1H), 7.75
J ¼ 8.8 Hz, 3H), 7.61 (d, J ¼ 8.7 Hz, 2H), 2.31 (t, J ¼ 7.4 Hz, 2H), 2.26 (s,
(d, J ¼ 6.0 Hz, 2H), 7.63 (d, J ¼ 7.9 Hz, 1H), 7.32 (t, J ¼ 8.0 Hz, 1H),
3H), 1.57 (d, J ¼ 6.9 Hz, 2H), 1.27 (s, 6H), 0.85 (d, J ¼ 6.6 Hz, 3H). 13
C
2.68e2.54 (m, 1H), 2.30 (s, 3H), 1.12 (d, J ¼ 6.8 Hz, 6H). 13C NMR
NMR (75 MHz, DMSO-d6) d: 178.6, 171.4, 147.5, 140.3, 132.0, 127.1,
(75 MHz, DMSO-d6) d: 179.0, 175.3, 147.7, 139.4, 138.1, 128.6, 121.3,
118.3 36.42, 31.0, 28.31, 25.0, 22.0, 13.9, 13.7. ESI-MS m/z ¼ 321.3
119.9, 117.1, 35.0, 19.5, 14.1. Anal. Calcd for C13H18N4OS: C, 56.09; H,
6.52; N, 20.13; found: C, 55.86; H, 6.40; N, 20.39. ESI-MS m/
z ¼ 279.2 [M þ 1]þ.
[M þ 1]þ.
4 . 2 . 2 . 1 0 . 1 - ( 4 - M e t h o x y f o r m a m i d o p h e n y l ) e t h y l -
idenethiosemicarbazide (7j). Yellowish solid product, yield 71%,
4.2.2.18. 1-(3-Pentanamidophenyl)ethylidenethiosemicarbazide (8d).
Solid product, yield 88%, m.p. 198e199 ꢀC, 1H NMR (300 MHz,
DMSO-d6) d: 10.32 (s, 1H), 9.90 (s, 1H), 8.39 (s, 1H), 7.94 (s, 1H), 7.72
m.p. 217e218 ꢀC. 1H NMR (300 MHz, DMSO-d6)
d
: 10.10 (s, 1H), 9.76
(s, 1H), 8.20 (s, 1H), 7.84 (d, J ¼ 7.8 Hz, 3H), 7.45 (d, J ¼ 8.1 Hz, 2H),
3.66 (s, 3H), 2.24 (s, 3H). 13C NMR (75 MHz, DMSO-d6)
: 178.6,
d
(d, J ¼ 7.5 Hz, 2H), 7.61 (d, J ¼ 7.7 Hz, 1H), 7.30 (t, J ¼ 7.9 Hz, 1H),
153.8, 147.6, 140.1, 131.5, 127.3, 117.4, 51.7, 13.7. ESI-MS m/z ¼ 267.3
2.40e2.20 (m, 5H), 1.64e1.48 (m, 2H), 1.38e1.23 (m, 2H), 0.89 (t,
[M þ 1]þ.
J ¼ 7.3 Hz, 3H). 13C NMR (75 MHz, DMSO-d6)
d: 179.0, 171.4, 147.7,
139.3, 138.1, 128.6, 121.3, 119.9, 117.0, 36.1, 27.2, 21.8, 14.1, 13.7. ESI-
4.2.2.11. 1-(4-Benzamidophenyl)ethylidenethiosemicarbazide (7k).
MS m/z ¼ 293.4 [M þ 1]þ.
Solid product, yield 82%, m.p. 140 ꢀC (dec.). 1H NMR (300 MHz,
DMSO-d6)
d
: 10.38 (s, 1H), 10.20 (s, 1H), 8.29 (s, 1H), 8.03e7.90 (m,
4.2.2.19. 1-(3-tert-Pentanamidophenyl)ethylidenethiosemicarbazide
5H), 7.83 (d, J ¼ 8.9 Hz, 2H), 7.68e7.49 (m, 3H), 2.30 (s, 3H). 13C NMR
(8e). Solid product, yield 84%, m.p. 220e221 ꢀC. 1H NMR (300 MHz,
(75 MHz, DMSO-d6)
d: 178.7, 165.6, 147.4, 140.2, 134.8, 132.6, 131.7,
DMSO-d6)
(d, J ¼ 7.8 Hz, 2H), 7.64 (d, J ¼ 7.8 Hz,1H), 7.31 (t, J ¼ 8.0 Hz,1H), 2.30
(s, 3H), 1.24 (s, 9H). 13C NMR (75 MHz, DMSO-d6)
: 178.9, 176.5,
147.8, 139.3, 137.9, 128.3, 121.4, 120.9, 118.2, 27.2, 14.1. Anal. Calcd for
d: 10.31 (s, 1H), 9.21 (s, 1H), 8.40 (s, 1H), 8.01 (s, 1H), 7.80
128.4, 127.7, 127.1, 119.5, 13.7. Anal. Calcd for C16H16N4OS: C, 61.52;
H, 5.16; N, 17.93; found: C, 61.31; H, 5.07; N, 18.04. ESI-MS m/
z ¼ 313.2 [M þ 1]þ.
d