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L. Maingot et al. / European Journal of Medicinal Chemistry 69 (2013) 244e261
(s, 1H), 7.35 (dt, J ¼ 9.0 Hz, J ¼ 2.0 Hz, 2H), 7.61 (s, 1H), 8.08 (t,
J ¼ 12.0 Hz, 1H, NH), 9.32 (s, 1H, NH), 10.08 (s, 1H, NH).
tR,LCMS ¼ 2.72 min, Purity 98.8%; MS (ESIþ) m/z ¼ 368 [M þ H]þ.
4.3.52. 4-Cyclohexylbutyl-1-(4-nitrophenoxyacethyl)-
thiosemicarbazide (39)
Synthesized following procedure D. White powder. Yield 68%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 0.75e0.88 (m, 2H), 1.05e
4.3.46. 1-(4-Chlorophenoxyacethyl)-4-phenylpropyl-
thiosemicarbazide (33)
1.30 (m, 8H), 1.39e1.49 (m, 2H), 1.55e1.69 (m, 5H), 3.36e3.46 (m,
2H), 4.77 (s, 2H), 7.20 (d, J ¼ 8.7 Hz, 2H), 7.99 (br s, 1H, NH), 8.21 (d,
J ¼ 8.7 Hz, 2H), 9.20 (s, 1H, NH), 10.10 (s, 1H, NH). tR,LCMS ¼ 3.77 min,
Purity 99.5%; MS (ESIþ) m/z ¼ 409 [M þ H]þ.
Synthesized following procedure D. White powder. Yield 88%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 1.74e1.84 (m, 2H), 2.50e
2.57 (m, 2H), 3.42e3.48 (m, 2H), 4.61 (s, 2H), 7.02 (d, J ¼ 8.6 Hz, 2H),
7.21e7.34 (m, 7H), 8.05 (br s, 1H, NH), 9.25 (s, 1H, NH), 10.05 (s, 1H,
NH). tR,LCMS ¼ 5.87 min (10 min gradient), Purity 98.5%, MS (ESIþ)
m/z ¼ 378 [M þ H]þ.
4.3.53. 4-Cyclohexylbutyl-1-(1-naphthyloxyacethyl)-
thiosemicarbazide (40)
Synthesized following procedure D. White powder. Yield 68%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 0.72e0.92 (m, 2H), 1.06e
4.3.47. 1-(4-Chlorophenoxyacethyl)-4-phenylbutyl-
thiosemicarbazide (34)
1.30 (m, 8H), 1.40e1.48 (m, 2H), 1.55e1.69 (m, 5H), 3.37e3.47 (m,
2H), 4.77 (s, 2H), 6.95 (d, J ¼ 7.7 Hz, 1H), 7.41 (dd, J ¼ 7.7 Hz,
J ¼ 7.7 Hz, 1H), 7.47e7.57 (m, 3H), 7.78 (d, J ¼ 7.7 Hz, 1H), 7.96 (br s,
1H, NH), 8.43 (d, J ¼ 7.7 Hz, 1H), 9.25 (s, 1H, NH), 10.08 (s, 1H, NH).
tR,LCMS ¼ 3.95 min, Purity 99.5%; MS (ESIþ) m/z ¼ 409 [M þ H]þ.
Synthesized following procedure D. White powder. Yield 92%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 1.45e1.52 (m, 4H), 2.55e
2.59 (t, J ¼ 6.9 Hz, 2H), 3.36 (s, 2H), 4.42e4.46 (m, 2H), 7.00 (d,
J ¼ 8.6 Hz, 2H), 7.15e7.34 (m, 7H), 8.00 (s, 1H, NH), 9.19 (s, 1H, NH),
10.01 (s, 1H, NH). tR,LCMS ¼ 6.52 min (10 min gradient), Purity 99.5%;
MS (ESIþ) m/z ¼ 392 [M þ H]þ.
4.3.54. 1-(6-Chloro-3,4-dihydro-2H-benzo [1,4]oxazin-2-
carbonyl)-4-(cyclohexylbutyl)-thiosemicarbazide (41)
Synthesized following procedure D. White powder. Yield 16%;
4.3.48. 1-(4-chlorophenoxyacethyl)-4-cyclohexylbutyl-
thiosemicarbazide (35)
1H NMR (300 MHz, CD3CN):
d (ppm): 0.87e0.94 (m, 2H), 1.11e1.20
(m, 8H), 1.41e1.52 (m, 2H), 1.69e1.73 (m, 5H), 3.45e3.51 (m, 4H),
4.75 (br s, 1H), 4.87 (t, J ¼ 8.3 Hz, 1H), 6.69 (d, J ¼ 8.5 Hz, 1H), 6.82
(dd, J ¼ 2.2 Hz, J ¼ 8.4 Hz, 2H), 6.93 (d, J ¼ 2.2 Hz, 1H), 7.66 (s, 1H),
8.74 (s, 1H). tR,LCMS ¼ 2.95 min, Purity 95%; MS (ESIþ) m/z ¼ 426
[M þ H]þ.
Synthesized following procedure D. White powder. Yield 78%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 0.81e0.88 (m, 2H), 1.10e
1.25 (m, 8H), 1.37e1.48 (m, 2H), 1.55e1.69 (m, 5H), 3.37e3.47 (m,
2H), 4.57 (s, 2H), 7.01 (d, J ¼ 8.7 Hz, 2H), 7.33 (d, J ¼ 8.7 Hz, 2H), 7.92
(br s, 1H, NH), 9.17 (s, 1H, NH), 10.00 (s, 1H, NH). 13C NMR 75 MHz
(DMSO):
d
(ppm): 24.0, 26.3, 26.7, 29.5, 33.4, 37.1, 37.5, 44.2; 67.7,
4.3.55. 1-(4-Biphenylacethyl)-4-cyclohexylbutyl-thiosemicarbazide
(42)
116.9, 125.3; 126.7, 157.1, 167.6. tR,LCMS ¼ 3.62 min, Purity 99.5%, MS
(ESIþ) m/z ¼ 398 [M þ H]þ.
Synthesized following procedure D. White powder; yield 79%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 0.75e0.93 (m, 2H), 1.13e
4.3.49. 4-Cyclohexylbutyl-1-(4-trifluoromethylphenoxyacethyl)-
thiosemicarbazide (36)
1.23 (m, 8H), 1.42e1.47 (m, 2H), 1.62e1.67 (m, 5H), 3.41 (m, 2H),
3.52 (s, 2H), 7.34e7.47 (m, 5H), 7.58e7.67 (m, 4H), 7.84 (br s, 1H,
NH), 9.15 (s, 1H, NH), 9.93 (s, 1H, NH). tR ¼ 6.75 min (10 min
gradient), Purity 99.5%; MS (ESIþ) m/z ¼ 424 [M þ H]þ.
Synthesized following procedure D. White powder. Yield 68%;
1H NMR (300 MHz, DMSO-d6):
d (ppm): 0.71e0.88 (m, 2H), 1.08e
1.31 (m, 8H), 1.37e1.51 (m, 2H), 1.55e1.69 (m, 5H), 3.35e3.45 (m,
2H), 4.68 (s, 2H), 7.17 (d, J ¼ 8.7 Hz, 2H), 7.65 (d, J ¼ 8.7 Hz, 2H), 7.95
(br s, 1H, NH), 9.17 (s, 1H, NH), 10.05 (s, 1H, NH). tR,LCMS ¼ 3.82 min,
Purity 99.5%; MS (ESIþ) m/z ¼ 432 [M þ H]þ.
4.3.56. 4-Cyclohexylbutyl-1-(phenyl-[1,2,4]oxadiazol-5-yl-acetyl)-
thiosemicarbazide (43)
Synthesized following procedure D. White powder. Yield 68%;
1H NMR (300 MHz, CDCl3):
d (ppm): 0.73e0.91 (m, 2H), 1.06e1.33
4.3.50. N-([(4-Cyclohexylbutyl)carbamothioyl]amino)-2-
phenoxyacetamide (37)
(m, 7H), 1.49e1.72 (m, 9H), 3.52e3.60 (m, 2H), 4.09 (s, 2H), 6.95 (br
s, 1H NH), 7.50e7.55 (m, 3H), 8.03e8.09 (m, 2H), 8.69 (s, 1H NH),
9.89 (s, 1H NH). tR,LCMS ¼ 5.97 min (10 min gradient), Purity 99% MS
(ESIþ) m/z ¼ 416 [M þ H]þ.
Synthesized following procedure D. White powder. Yield 52%;
1H NMR 300 MHz (DMSO-d6):
d (ppm) 0.83e0.92 (m, 2H), 1.24e
1.45 (m, 8H), 1.40e1.50 (m, 2H), 1.61e1.68 (m, 5H), 4.36e4.40 (m,
2H), 4.56 (s, 2H), 6.98 (d, 3H, J ¼ 7.8 Hz), 7.30 (t, 2H, J ¼ 8.7 Hz), 7.91
(br s, 1H), 9.18 (br s, 1H), 10.0 (br s, 1H). 13C NMR 75 MHz (DMSO-
4.3.57. 4-(Cyclohexylbutyl)-1-(3-pyrazin-2-yl-[1,2,4]oxadiazol-5-
yl-acetyl)-thiosemicarbazide (44)
d6):
d
(ppm) 24.0, 26.3, 26.7, 29.5, 33.3, 37.2, 37.4, 44.2, 66.5, 115.1,
Synthesized following procedure D. White powder. Yield 50%;
121.6, 129.9, 158.2, 167.8, 181.8. tR,LCMS ¼ 3.48 min, (5 min gradient),
1H NMR (DMSO-d6):
d (ppm): 0.75e0.83 (m, 2H), 1.11e1.23 (m, 8H),
Purity 95%; MS (ESIþ) m/z ¼ 364 [M þ H]þ. HRMS m/z calculated for
1.60e1.66 (m, 7H), 3.45e3.50 (m, 2H), 4.16 (s, 2H), 8.03 (br s, NH),
8.88 (d, J ¼ 2.4 Hz, 2H), 9.26 (s, 1H), tR,LCMS ¼ 3.46 min, MS (ESIþ) m/
z ¼ 418 [M þ H]þ.
C
19H28N3OS [M ꢃ H2O þ H]þ 346.1953, found 346.1949.
4.3.51. N-([(4-Cyclohexylbutyl)carbamothioyl]amino)-2-(4-
methoxyphenoxy)acetamide (38)
4.3.58. N-([(4-Cyclohexylbutyl)carbamothioyl]amino)acetamide
(45)
Synthesized following procedure D. White powder. Yield 56%;
1H NMR 300 MHz (DMSO-d6):
d
(ppm) 0.75e1.07 (m, 2H), 1.16e1.24
Synthesized following procedure D. White powder. Yield 17%;
(m, 8H), 1.39e1.49 (m, 2H), 1.61e1.68 (m, 5H), 3.36e3.42 (m, 2H),
3.69 (s, 3H), 4.49 (s, 2H), 6.81e6.94 (m, 4H), 7.87 (br s,1H), 9.16 (br s,
1H NMR 300 MHz (DMSO-d6):
d
(ppm) 0.76e0.89 (m, 2H), 1.07e
1.20 (m, 8H), 1.39e1.46 (m, 2H), 1.63e1.68 (m, 5H), 1.64 (s, 3H),
3.37e3.39 (m, 2H), 7.86 (br s, 1H), 8.99 (br s, 1H), 9.59 (br s, 1H). 13
NMR 75 MHz (DMSO-d6): (ppm) 21.4, 24.0, 26.3, 26.7, 29.5, 33.3,
1H), 9.95 (br s,1H). 13C NMR 75 MHz (DMSO-d6):
d
(ppm) 24.0, 26.3,
C
26.7, 29.5, 33.3, 37.2, 37.4, 44.2, 55.8, 67.2, 115.0, 116.1, 152.2, 154.2,
168.0, 182.1. tR,LCMS ¼ 3.43 min, (5 min gradient), Purity 100%; MS
(ESIþ) m/z ¼ 394 [M þ H]þ. HRMS m/z calculated for C20H32N3O3S
[M þ H]þ 394.2164, found 394.2177.
d
37.1, 37.5, 44.1, 169.4, 181.8. tR,LCMS ¼ 3.13 min (5 min gradient),
Purity 93%; MS (ESIþ) m/z ¼ 272 [M þ H]þ. HRMS m/z calculated for
C
13H26N3OS [M þ H]þ 272.1797, found 272.1805.