N-Methylthioureas as Novel ROR
α
Agonists
1395
1557, 1509, 1345, 1296, 1223, 1157, 1081, 1016, 964, 822 3242, 2923, 1571, 1511, 1458, 1348, 1293, 1219, 1174,
cm−1; FAB-MS (m/z): 199 [M+H]+; 1H-NMR (300 MHz, 1108, 948, 848, 736 cm−1; FAB-MS (m/z): 226 [M+H]+;
CD3OD)
δ
7.35-7.30 (m, 2H), 7.05-6.99 (m, 2H), 4.68 (s, 1H-NMR (300 MHz, DMSO)
δ
8.18 (d,
8.07 (s, 1H), 7.67 (s, 1H), 7.51 (d, = 8.4 Hz, 2H), 4.79
(s, 2H), 2.83 (s, 3H) ppm; 13C-NMR (100 MHz, DMSO)
183.7, 148.0, 146.3, 128.6, 1223.8, 46.4, 30.9 ppm.
J = 8.4 Hz, 2H),
2H), 2.93 (s, 3H) ppm; 13C-NMR (75 MHz, CD3OD)
165.1, 161.8, 136.1, 130.4, 116.2, 72.0, 31.0 ppm.
δ
J
δ
1-(3,4-Difluoro-benzyl)-3-methyl-thiourea (8)
White solid; yield 55%; m.p. 122oC; IR (KBr) 3255, 1-(4-Dimethylamino-benzyl)-3-methyl-thiourea (14)
1611, 1558, 1519, 1437, 1344, 1286, 1210, 1115, 966, Yellow solid; yield 47%; m.p. 89oC; IR (KBr) 3261,
816, 778 cm−1; FAB-MS (m/z): 217 [M+H]+; H-NMR 2936, 1615, 1555, 1523, 1345, 1287, 1228, 1190, 1166,
1
(400 MHz, DMSO)
δ
7.97 (s, 1H), 7.52 (s, 2H), 7.40- 1064, 1018, 947, 807, 752 cm−1; FAB-MS (m/z): 223
7.29 (m, 2H), 7.13 (s, 1H), 4.63 (s, 2H), 2.83 (s, 3H) [M+H]+; H-NMR (400 MHz, DMSO)
δ
7.73 (s, 1H),
= 6.3 Hz, 2H), 6.68 (d, = 6.45
Hz, 2H), 4.49 (s, 2H), 2.87-2.83 (m, 9H) ppm; 13C-NMR
(100 MHz, DMSO) 149.7, 128.4, 126.8, 112.4, 46.8,
40.3, 31.2, 30.9 ppm.
1
ppm; 13C-NMR (100 MHz, DMSO)
δ
183.7, 150.4, 7.33 (s, 1H), 7.13 (d,
J
J
148.0, 137.6, 123.9, 117.2, 45.8, 30.7 ppm.
δ
1-(2,4-Difluoro-benzyl)-3-methyl-thiourea (9)
Yellow solid; yield 99%; m.p. 119oC; IR (KBr) 3225,
1569, 1505, 1428, 1375, 1353, 1272, 1231, 1137, 1103, 1-Methyl-3-(4-methyl-benzyl)-thiourea (15)
1078, 966, 859, 746 cm−1; FAB-MS (m/z): 217 [M+H]+; White solid; yield 69%; m.p. 116oC; IR (KBr) 3245,
1H-NMR (400 MHz, CD3OD)
δ 7.40 (dd, J1 = 14.84 Hz, 3021, 2924, 2103, 1557, 1516, 1454, 1344, 1295, 1229,
J2 = 8.00 Hz, 1H), 6.93-6.88 (m, 2H), 4.72 (s, 2H), 2.94 1083, 1020, 963, 930, 802, 747 cm−1; FAB-MS (m/z):
(s, 3H) ppm; 13C-NMR (100 MHz, CD3OD)
164.1, 163.3, 161.7, 132.5, 124.0, 112.9, 42.9, 31.5 ppm. (m, 4H), 6.29 (s, 2H), 4.67 (s, 2H), 3.02 (d,
δ
165.7, 195 [M+H]+; H-NMR (300 MHz, CDCl3)
δ
J
7.36-7.21
= 4.2 Hz,
1
3H), 2.42 (s, 3H) ppm; 13C-NMR (100 MHz, CDCl3)
δ
1-(4-Chloro-benzyl)-3-methyl-thiourea (10)
182.3, 137.6, 133.8, 129.5, 127.5, 48.2, 30.8, 21.0 ppm.
White solid; yield 71%; m.p. 110oC; IR (KBr) 3255,
3062, 1557, 1492, 1343, 1292, 1091, 1014, 964, 931, 1-Methyl-3-(3-methyl-benzyl)-thiourea (16)
1
802 cm−1; FAB-MS (m/z): 215 [M+H]+; H-NMR (300 White solid; yield 99%; m.p. 77oC; IR (KBr) 3254, 3060,
MHz, CDCl3)
2H), 2.96 (d,
MHz, CDCl3)
30.75 ppm.
δ
7.32-7.24 (m , 4H), 5.96 (s, 2H), 4.68 (s, 2920, 1607, 1557, 1463, 1341, 1295, 1223, 1081, 1024,
= 4.59 Hz, 3H) ppm; 13C-NMR (100 959, 776, 742, 692 cm−1; FAB-MS (m/z): 195 [M+H]+;
182.55, 135.71, 133.51, 128.87, 47.69, 1H-NMR (300 MHz, CDCl3)
7.40-7.33 (m, 2H), 7.24-
7.21 (m, 2H), 6.34 (s, 2H), 4.73 (s, 2H), 3.07 (d,
4.59 Hz, 3H), 2.46 (s, 3H) ppm; 13C-NMR (100 MHz,
CDCl3) 182.50, 138.69, 136.91, 128.80, 128.67, 128.33,
J
δ
δ
J
=
1-(3,4-Dichloro-benzyl)-3-methyl-thiourea (11)
δ
White solid; yield 39%; m.p. 136oC; IR (KBr) 3230, 124.64, 48.51, 30.88, 21.40 ppm.
1557, 1515, 1471, 1299, 1205, 1130, 1030, 961, 824
cm−1; FAB-MS (m/z): 249 [M+H]+; 1H-NMR (300 MHz, 1-Methyl-3-(2-methyl-benzyl)-thiourea (17)
CD3OD)
= 2.01 Hz, 1H), 4.70 (s, 2H), 2.81 (s, 3H) ppm; 13C- 1556, 1461, 1344, 1298, 1078, 1020, 962, 746 cm−1;
NMR (100 MHz, CD3OD)
183.2, 142.2, 132.8, 130.0, FAB-MS (m/z): 195 [M+H]+; 1H-NMR (400 MHz,
δ
7.47-7.42 (m, 2H), 7.23 (dd, J1 = 9.15 Hz, J2 White solid; yield 99%; m.p. 90oC; IR (KBr) 3245, 3064,
δ
126.8, 126.5, 125.8, 46.3, 30.6 ppm.
CD3OD)
2.27 (s, 3H) ppm; 13C-NMR (100 MHz, CD3OD)
183.25, 137.06, 135.51, 129.90, 126.82, 125.72, 45.28,
δ 7.18-7.14 (m, 4H), 4.60 (s, 2H), 2.86 (s, 3H),
δ
1-(2,4-Dichloro-benzyl)-3-methyl-thiourea (12)
White solid; yield 94%; m.p. 110oC; IR (KBr) 3256, 30.92, 18.71 ppm.
3062, 1556, 1297, 1102, 1049, 965, 938, 865, 830, 755
cm−1; FAB-MS (m/z): 250 [M+H]+; 1H-NMR (300 MHz, 1-(4-tert-Butyl-benzyl)-3-methyl-thiourea (18)
CDCl3)
δ 7.42 (d, J
= 2.01 Hz, 1H), 7.35-7.25 (m, 2H), White solid; yield 99%; m.p. 78oC; IR (KBr) 3255, 2961,
4.76 (s, 2H), 2.95 (s, 3H) ppm; 13C-NMR (75 MHz, 1558, 1515, 1465, 1343, 1295, 1081, 1018, 964, 935, 818,
1
CDCl3)
46.9, 32.0 ppm.
δ
173.8, 137.2, 135.6, 135.2, 131.9, 130.8, 128.9, 755 cm−1; FAB-MS (m/z): 237 [M+H]+; H-NMR (300
MHz, CDCl3)
Hz, 2H), 5.86 (s, 2H), 4.61 (s, 2H), 2.96 (d,
1.3 (s, 9H) ppm; 13C-NMR (100 MHz, CDCl3)
δ
7.37 (d,
J
= 8.2 Hz, 2H), 7.24 (d,
= 4.6 Hz, 3H),
182.7,
J = 8.1
J
1-Methyl-3-(4-nitro-benzyl)-thiourea (13)
δ
Yellow solid; yield 89%; m.p. 155oC; IR (KBr) 3378, 151.1, 133.7, 127.4, 126.1, 48.3, 34.5, 31.8, 30.8 ppm.