K.-w. Jeong et al. / European Journal of Medicinal Chemistry 102 (2015) 387e397
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4.15.5. N-(4-((4-(3-Hydroxyphenyl)thiazol-2-yl)amino)phenyl)
1H), 7.89 (d, J ¼ 1.8 Hz,1H), 7.56 (d, J ¼ 8.1 Hz, 1H), 7.32 (t, J ¼ 2.0 Hz,
1H), 7.26e7.20 (m, 2H), 7.12 (s, 1H), 6.96 (s, 1H), 6.76 (dd, J ¼ 8.2,
acetamide (9c)
MP: 201.3 ꢀC; 1H NMR (400 MHz, DMSO)
d
10.17 (s, 1H), 9.86 (s,
1.7 Hz, 1H), 2.06 (s, 3H); 13C NMR (100 MHz, DMSO)
d 168.75,
1H), 7.66e7.60 (m, 2H), 7.54 (d, J ¼ 8.9 Hz, 2H), 7.36e7.30 (m, 2H),
163.13, 151.06, 145.68, 145.57, 142.06, 140.30, 129.57, 126.93, 117.81,
116.07, 113.90, 112.52, 112.13, 108.02, 100.30, 24.57; LRMS (ESI) m/z:
342.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for [MþH]þ C17H15N3O3S:
342.0907; found: 342.0908.
7.23e7.17 (m, 2H), 6.70 (dd, J ¼ 7.9,1.6 Hz,1H), 2.03 (s, 3H); 13C NMR
(100 MHz, DMSO)
d 168.26, 163.48, 158.00, 150.65, 137.20, 136.30,
133.71, 130.02, 120.30, 117.67, 116.91, 115.04, 113.17, 102.87, 24.34;
LRMS (ESI) m/z: 326.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for [MþH]þ
C17H15N3O2S: 326.0958; found: 326.0955.
4.15.12. 4-(2-(Phenylamino)thiazol-4-yl)benzene-1,2-diol (9j)
MP: 244.8 ꢀC; 1H NMR (400 MHz, DMSO)
d
9.94 (s, 1H), 7.40 (s,
2H), 7.03 (s, 2H), 6.88 (s, 1H), 6.66 (s, 1H), 6.46 (s, 1H); 13C NMR
(100 MHz, DMSO) 164.33, 148.68, 146.17, 145.73, 141.04, 129.64,
4.15.6. N-(4-((4-Phenylthiazol-2-yl)amino)phenyl)acetamide (9d)
MP: 286.4 ꢀC; 1H NMR (400 MHz, DMSO)
d
10.19 (s, 1H), 9.85 (s,
d
1H), 7.91 (d, J ¼ 8.2 Hz, 2H), 7.63 (d, J ¼ 9.0 Hz, 2H), 7.54 (d,
125.39, 122.69, 118.23, 117.71, 116.28, 114.04, 100.33; LRMS (ESI) m/
z: 285.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for [MþH]þ C15H13N2O2S:
285.0692; found: 285.0690.
J ¼ 8.2 Hz, 2H), 7.43 (t, J ¼ 7.7 Hz, 2H), 7.33e7.28 (m, 2H), 2.02 (s,
3H); 13C NMR (100 MHz, DMSO)
d 168.39, 162.58, 147.54, 136.41,
134.34, 133.94, 129.12, 128.81, 128.42, 126.24, 120.35, 118.21, 103.12,
90.10, 24.33; LRMS (ESI) m/z: 310.1 [MþH]þ; HRMS (ESI) m/z: Calcd.
for [MþH]þ C17H16N3OS: 310.1009; found: 310.1011.
4.15.13. N-(4-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)
phenyl)propionamide (19a)
MP: 209.1 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.07 (s, 1H), 9.76 (s,
4.15.7. N-(4-((4-(3,4-Dimethoxyphenyl)thiazol-2-yl)amino)phenyl)
1H), 8.99 (s, 1H), 7.62 (d, J ¼ 8.9 Hz, 1H), 7.54 (d, J ¼ 9.0 Hz, 2H), 7.32
(d, J ¼ 2.0 Hz, 1H), 7.18 (dd, J ¼ 8.2, 2.1 Hz, 1H), 6.93 (s, 1H), 6.76 (d,
J ¼ 8.2 Hz, 1H), 2.30 (q, J ¼ 15.3, 7.7 Hz, 2H), 1.09 (t, J ¼ 7.6 Hz, 3H);
acetamide (9e)
MP: 231.4 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.15 (s, 1H), 9.84 (s,
1H), 7.60 (d, J ¼ 9.0 Hz, 2H), 7.53 (d, J ¼ 9.1 Hz, 2H), 7.50e7.44 (m,
13C NMR (100 MHz, DMSO)
d 171.97, 163.30, 151.00, 145.65, 145.56,
2H), 7.18 (s, 1H), 7.01 (d, J ¼ 8.4 Hz, 1H), 3.83 (s, 3H), 3.78 (s, 3H),
137.24, 133.64, 126.94, 120.31, 117.60, 117.52, 116.14, 113.92, 99.86,
29.90, 10.28; LRMS (ESI) m/z: 356.1 [MþH]þ; HRMS (ESI) m/z: Calcd.
for [MþH]þ C18H18N3O3S: 356.1063; found: 356.1066.
2.02 (s, 3H); 13C NMR (100 MHz, DMSO)
d 168.25, 163.57, 150.51,
149.16, 148.96, 137.22, 133.73, 128.16, 120.37, 118.84, 117.76, 112.27,
109.81, 101.08, 55.96, 55.93, 24.32; LRMS (ESI) m/z: 370.1 [MþH]þ;
HRMS (ESI) m/z: Calcd. for [MþH]þ C19H20N3O3S: 370.1220; found:
370.1219.
4.15.14. N-(4-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)
phenyl)isobutyramide (19b)
MP: 213.4 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.07 (s, 1H), 9.73 (s,
4.15.8. N-(4-((4-(3,4-Difluorophenyl)thiazol-2-yl)amino)phenyl)
acetamide (9f)
1H), 8.99 (s, 2H), 7.61 (d, J ¼ 9.1 Hz, 2H), 7.56 (d, J ¼ 9.1 Hz, 2H), 7.32
(d, J ¼ 2.1 Hz, 1H), 7.18 (dd, J ¼ 8.2, 2.1 Hz, 1H), 6.93 (s, 1H),
6.80e6.74 (m, 1H), 2.57 (dt, J ¼ 13.6, 6.8 Hz, 2H), 1.10 (d, J ¼ 6.8 Hz,
MP: 204.6 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.22 (s, 1H), 9.85 (s,
1H), 7.93 (dd, J ¼ 12.2, 7.9, 2.1 Hz, 1H), 7.81e7.75 (m, 1H), 7.61 (d,
5H); 13C NMR (175 MHz, DMSO)
d 175.21, 163.35, 151.02, 145.68,
J ¼ 9.0 Hz, 2H), 7.54 (d, J ¼ 9.0 Hz, 2H), 7.49 (dt, J ¼ 10.5, 8.6 Hz, 1H),
145.59, 137.27, 133.71, 126.96, 120.46, 117.63, 117.55, 116.15, 113.94,
99.89, 35.28, 20.07; LRMS (ESI) m/z: 370.1 [MþH]þ; HRMS (ESI) m/z:
Calcd. for [MþH]þ C19H20N3O3S: 370.1220; found: 370.0817.
7.40 (s, 1H), 2.02 (s, 3H); 13C NMR (100 MHz, DMSO)
d 168.27,
163.96, 151.35, 148.36, 148.10, 136.96, 133.89, 132.70, 122.92, 120.36,
118.22 (d, J ¼ 17 Hz) 118.14, 117.86, 114.85 (d, J ¼ 19 Hz), 104.15,
24.33; LRMS (ESI) m/z: 346.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for
[MþH]þ C17H14F2N3OS: 346.0820; found: 346.0818.
4.15.15. N-(4-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)
phenyl)benzamide (19c)
MP: 234.9 ꢀC; 1H NMR (400 MHz, DMSO)
d
10.17 (d, J ¼ 14.3 Hz,
4.15.9. N-(4-((4-(4-Hydroxy-3-methoxyphenyl)thiazol-2-yl)amino)
2H), 9.01 (d, J ¼ 3.6 Hz, 2H), 7.98e7.92 (m, 2H), 7.77e7.66 (m, 4H),
7.60e7.50 (m, 3H), 7.34 (d, J ¼ 2.1 Hz, 1H), 7.20 (dd, J ¼ 8.2, 2.1 Hz,
1H), 6.96 (s, 1H), 6.77 (d, J ¼ 8.2 Hz, 1H); 13C NMR (100 MHz, DMSO)
phenyl)acetamide (9g)
MP: 218.9 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.12 (s, 1H), 9.84 (s,
1H), 7.60 (d, J ¼ 9.0 Hz, 2H), 7.52 (d, J ¼ 9.1 Hz, 2H), 7.43 (d,
J ¼ 1.9 Hz, 1H), 7.35 (dd, J ¼ 8.2, 1.8 Hz, 1H), 7.08 (s, 1H), 6.81 (d,
J ¼ 8.2 Hz, 1H), 3.84 (s, 3H), 2.02 (s, 3H); 13C NMR (100 MHz, DMSO)
d 165.63, 163.22, 151.03, 145.68, 145.58, 137.88, 135.59, 133.24,
131.85, 128.82, 128.03, 126.93, 121.73, 117.54, 117.42, 116.16, 113.93,
100.02; LRMS (ESI) m/z: 403.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for
[MþH]þ C22H18N3O3S: 404.1063; found: 404.1064.
d
168.24, 163.47, 150.87, 148.02, 146.85, 137.26, 133.67, 126.89,
120.37, 119.21, 117.71, 115.99, 110.28, 100.23, 56.05, 24.32; LRMS
(ESI) m/z: 356.1 [MþH]þ; HRMS (ESI) m/z: Calcd. for [MþH]þ
C18H18N3O3S: 356.1063; found: 356.1066.
4.15.16. 3-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)benzoic
acid (20a)
MP: 297.4 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.42 (s, 1H), 8.25 (s,
4.15.10. N-(4-((4-(3-Hydroxy-4-methoxyphenyl)thiazol-2-yl)
1H), 8.07 (d, J ¼ 8.0 Hz, 1H), 7.57e7.41 (m, 2H), 7.31 (d, J ¼ 2.1 Hz,
amino)phenyl)acetamide (9h)
1H), 7.22 (dd, J ¼ 8.2, 2.0 Hz,1H), 7.02 (s, 1H), 6.77 (d, J ¼ 8.2 Hz,1H);
MP: 215.6 ꢀC; 1H NMR (400 MHz, DMSO)
d
10.12 (s, 1H), 9.86 (s,
13C NMR (100 MHz, DMSO)
d 168.08, 162.85, 151.05, 145.76, 145.62,
1H), 7.62 (d, J ¼ 8.9 Hz, 2H), 7.57e7.50 (m, 2H), 7.35 (s, 1H), 7.31 (d,
141.90, 132.47, 129.62, 126.83, 122.20, 120.93, 117.96, 117.71, 116.07,
113.88, 100.72; LRMS (ESI) m/z: 329.1 [MþH]þ; HRMS (ESI) m/z:
Calcd. for [MþH]þ C16H13N2O4S: 329.0591; found: 329.0592.
J ¼ 8.4 Hz, 1H), 7.03 (s, 1H), 6.95 (d, J ¼ 8.4 Hz, 1H), 3.79 (s, 3H), 2.02
(s, 3H); 13C NMR (100 MHz, DMSO)
d 168.24, 163.38, 150.61, 147.84,
146.85, 137.26, 133.64, 128.32, 120.29, 117.61, 117.26, 113.69, 112.69,
100.75, 56.07, 24.33; LRMS (ESI) m/z: 356.1 [MþH]þ; HRMS (ESI) m/
z: Calcd. for [MþH]þ C18H18N3O3S: 356.1063; found: 356.1066.
4.15.17. 4-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)benzoic
acid (20b)
MP: 294.8 ꢀC; 1H NMR (400 MHz, DMSO)
d 10.68 (s, 1H), 7.92
4.15.11. N-(3-((4-(3,4-Dihydroxyphenyl)thiazol-2-yl)amino)
(dd, J ¼ 8.8, 2.1 Hz, 2H), 7.82 (dd, J ¼ 8.6, 2.3 Hz, 2H), 7.35 (s,1H), 7.21
phenyl)acetamide (9i)
(dd, J ¼ 8.2, 2.0 Hz, 1H), 7.08 (s, 1H), 6.78 (dd, J ¼ 8.1, 2.8 Hz, 1H); 13
C
MP: 224.9 ꢀC; 1H NMR (400 MHz, DMSO)
d
10.24 (s, 1H), 9.97 (s,
NMR (100 MHz, DMSO) d 167.67, 162.29, 151.16, 145.83, 145.66,