432
L. Xiong et al. / European Journal of Medicinal Chemistry 95 (2015) 424e434
1H), 7.13e7.11 (m, 1H), 4.63 (s, 2H), 3.99 (s, 3H); 13C NMR
(150 MHz,CDCl3) 164.86, 159.55, 150.77, 149.07, 148.90, 142.12,
4.5.17. Data for 15a
d
White solid; yield: 62%; mp 95e97 ꢁC; 1H NMR (600 MHz,
135.18, 134.43, 133.19, 125.47, 118.08, 117.50, 117.28, 116.79, 113.23,
111.69, 110.86, 110.14, 109.99, 109.81, 39.55, 35.37; HRMS (MALDI):
Calcd for C20H15F3N4O2S [MþH]þ 433.0946. Found: 433.0939.
CDCl3)
1H), 7.53 (s, 1H), 7.47 (s, 1H), 7.38 (s, 1H), 7.36 (d, J ¼ 4.2 Hz,1H), 4.51
(s, 2H), 3.99 (s, 3H); 13C NMR (151 MHz, CD3OD-d6)
167.07, 161.80,
150.39, 143.46, 142.39, 140.71, 137.04, 135.81, 135.31, 131.66, 130.57,
129.41, 128.99, 119.15, 118.33, 112.19, 111.26, 40.41 (s), 36.79 (s);
HRMS (MALDI): Calcd for C20H14ClF3N4O2S [MþH]þ 467.0556.
Found: 467.0562.
d 10.27 (s, 1H), 8.54 (s, 1H), 8.06 (s, 1H), 7.94 (s, 1H), 7.91 (s
d
4.5.11. Data for 12a
White solid; yield: 74%; mp 108e110 ꢁC; 1H NMR (400 MHz,
DMSO-d6)
d 10.27 (s, 1H), 8.53 (s, 1H), 8.05 (s, 1H), 7.75 (s, 1H), 7.61
(d, J ¼ 8.8 Hz,1H), 7.53 (d, J ¼ 7.6 Hz, 2H), 7.48 (d, J ¼ 7.6 Hz,1H), 7.31
(t, J ¼ 7.6 Hz, 1H), 4.61 (s, 2H), 4.00 (s, 3H); 13C NMR (150 MHz,
4.5.18. Data for 15b
CDCl3)
d
165.08, 158.81, 148.96, 142.08, 138.82, 138.57, 138.19,
White solid; yield: 66%; mp 151e152 ꢁC; 1H NMR (600 MHz,
135.06, 133.98, 131.95, 130.98, 130.22, 127.68, 122.52, 121.78, 119.99,
117.19,116.94,110.99,109.76, 39.78, 35.67; HRMS (MALDI): Calcd for
C
DMSO-d6) d 10.25 (s, 1H), 8.25 (s, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.47
(s,1H), 7.43 (d, J ¼ 8.4 Hz,1H), 7.39e7.35 (m, 2H), 7.27 (s,1H), 6.92 (t,
20H14BrF3N4O2S [MþNa]þ 551.0051. Found: 551.0058.
J ¼ 54.6 Hz,1H), 4.52 (s, 2H), 3.96 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
165.00, 159.37, 148.82, 142.84, 142.04, 137.94, 135.35, 134.42,
4.5.12. Data for 12b
129.94, 129.09, 128.07, 127.22, 117.10, 116.84, 113.29, 111.71, 110.73,
109.97, 39.61, 35.78; HRMS (MALDI): Calcd for C20H15ClF2N4O2S
[MþH]þ 449.0651. Found: 449.0648.
White solid; yield: 67%; mp 145e146 ꢁC; 1H NMR (400 MHz,
DMSO-d6)
d 10.15 (s, 1H), 8.49 (s, 1H), 8.05 (s, 1H), 7.75 (s, 1H), 7.63
(d, J ¼ 8.4 Hz, 1H), 7.54 (d, J ¼ 6.4 Hz, 2H), 7.35 (m, 2H), 7.33 (t,
J ¼ 53.6 Hz,1H), 4.61 (s, 2H), 3.98 (s, 3H); 13C NMR (150 MHz, CDCl3)
4.5.19. Data for 16a
d
164.93, 159.50, 148.81, 143.07, 142.88, 142.08, 138.21, 135.00,
White solid; yield: 76%; mp 139e140 ꢁC; 1H NMR (600 MHz,
134.32, 131.94, 130.95, 130.20, 127.67, 122.50, 116.92, 116.63, 113.10,
111.55, 110.80, 110.00, 109.82, 39.50, 35.67; HRMS (MALDI): Calcd
for C20H15BrF2N4O2S [MþH]þ 493.0145. Found: 493.0152.
DMSO-d6)
d
10.29 (s,1H), 8.55 (s, 1H), 8.06 (s, 1H), 7.63 (d, J ¼ 9.0 Hz,
1H), 7.54 (d, J ¼ 9.0 Hz,1H), 7.40 (d, J ¼ 7.8 Hz, 2H), 7.16 (d, J ¼ 7.8 Hz,
2H), 4.58 (s, 2H), 4.01 (s, 3H), 2.27 (s, 3H); 13C NMR (150 MHz,
CDCl3)
d 165.64, 159.10, 148.69, 141.82, 139.75, 139.32, 137.71,
4.5.13. Data for 13a
134.39, 133.92, 132.32, 129.35, 128.86, 121.69, 119.91, 117.41, 116.77,
110.94, 109.54, 39.59 36.21, 21.03; HRMS (MALDI): Calcd for
C
White solid; yield: 65%; mp 163e165 ꢁC; 1H NMR (600 MHz,
DMSO-d6)
d
10.29 (s,1H), 8.55 (s, 1H), 8.08 (s,1H), 7.68 (d, J ¼ 8.4 Hz,
21H17F3N4O2S [MþH]þ 447.1103. Found: 447.1095.
2H), 7.63 (d, J ¼ 9.0 Hz, 1H), 7.53 (dd, J ¼ 8.4, 1.8 Hz, 1H), 7.36 (d,
J ¼ 7.8 Hz, 2H), 4.65 (s, 2H), 4.01 (s, 3H); 13C NMR (150 MHz, CDCl3)
4.5.20. Data for 16b
d
165.17, 158.77, 148.84,148.67, 142.10,138.73,138.49, 135.18,134.74,
White solid; yield: 54%; mp 117e119 ꢁC; 1H NMR (600 MHz,
134.03, 130.51, 121.81, 121.13, 120.95, 120.03, 119.47, 117.20, 110.97,
109.96, 109.79, 39.78, 35.53; HRMS (MALDI): Calcd for
C
DMSO-d6) d 10.17 (s, 1H), 8.50 (s, 1H), 8.06 (s, 1H), 7.63 (s, 1H), 7.62
(d, J ¼ 8.4 Hz, 1H), 7.53 (d, J ¼ 8.4 Hz, 1H), 7.40 (d, J ¼ 7.8 Hz, 2H),
21H14F6N4O2S [MþH]þ 517.0769. Found: 517.0774.
7.36 (t, J ¼ 54.6 Hz, 1H), 4.58 (s, 2H), 3.98 (s, 3H), 2.27 (s, 3H); 13C
NMR (100 MHz, DMSO-d6)
d 164.47, 159.89, 147.58, 141.44, 136.96,
4.5.14. Data for 13b
133.34, 132.85, 129.08, 129.00, 116.87, 116.14, 109.79, 35.40, 20.63;
HRMS (MALDI): Calcd for C21H18F2N4O2S [MþH]þ 429.1197. Found:
429.1204.
White solid; yield: 45%; mp 111e113 ꢁC; 1H NMR (600 MHz,
DMSO-d6)
d
10.18 (s, 1H), 8.51 (s, 1H), 8.09 (s, 1H), 7.68 (d, J ¼ 8.4 Hz,
2H), 7.64 (d, J ¼ 9.0 Hz,1H), 7.54 (d, J ¼ 9.0 Hz,1H), 7.37 (d, J ¼ 7.8 Hz,
2H), 7.36 (t, J ¼ 54.0 Hz, 1H), 4.64 (s, 2H), 3.98 (s, 3H); 13C NMR
4.5.21. Data for 17a
(150 MHz, DMSO-d6)
d
165.07, 159.51, 148.75, 143.03, 141.99, 135.15,
White solid; yield: 59%; mp 121e123 ꢁC; 1H NMR (400 MHz,
134.72, 134.41, 130.51, 121.12, 119.46, 117.14, 116.74, 113.17, 111.62,
110.74, 110.08, 109.76, 39.56, 35.52; HRMS (MALDI): Calcd for
C
DMSO-d6)
(d, J ¼ 5.2 Hz,1H), 7.53 (d, J ¼ 8.8 Hz,1H), 7.42 (t, J ¼ 6.8 Hz, 2H), 4.61
(s, 2H), 4.01 (s, 3H). 13C NMR (150 MHz, CDCl3)
164.99, 158.69,
150.80, 149.02, 142.08, 135.45, 134.06, 133.12, 125.21, 121.84, 120.05,
118.07, 117.49, 117.31, 110.97, 109.86, 39.86, 35.37; HRMS (MALDI):
Calcd for C20H13F5N4O2S [MþH]þ 469.0758. Found: 469.0760.
d 10.28 (s, 1H), 8.55 (s, 1H), 8.07 (s, 1H), 7.64 (s, 1H), 7.61
21H15F5N4O2S [MþH]þ 499.0863. Found: 499.0857.
d
4.5.15. Data for 14a
White solid; yield: 62%; mp 166e168 ꢁC; 1H NMR (400 MHz,
DMSO-d6)
d
10.27 (s,1H), 8.54 (s,1H), 8.05 (d, J ¼ 1.6 Hz,1H), 7.62 (d,
J ¼ 8.8 Hz, 1H), 7.53 (d, J ¼ 1.6 Hz, 1H), 7.44 (d, J ¼ 8.4 Hz, 2H), 6.91
4.5.22. Data for 17b
(d, J ¼ 8.4 Hz, 2H), 4.57 (s, 2H), 4.00 (s, 3H), 3.73 (s, 3H); 13C NMR
White solid; yield: 49%; mp 142e144 ꢁC; 1H NMR (400 MHz,
(150 MHz, CDCl3)
d
165.71, 159.20, 158.87, 148.84, 142.17, 138.73,
DMSO-d6)
d
10.17 (s, 1H), 8.51 (s, 1H), 8.09 (d, J ¼ 1.6 Hz, 1H), 7.65 (d,
134.82, 133.90, 130.26, 127.48, 121.77, 119.98, 117.12, 114.05, 110.94,
109.65, 55.20, 39.70, 36.08; HRMS (MALDI): Calcd for
J ¼ 5.6 Hz, 1H), 7.62e7.60 (m, 1H), 7.55 (dd, J ¼ 8.8, 2.0 Hz, 1H),
7.43e7.40 (m, 2H), 7.37 (t, J ¼ 54 Hz, 1H), 4.62 (s, 2H), 3.99 (s, 3H);
C
21H17F3N4O3S [MþNa]þ 485.0871. Found: 485.0868.
13C NMR (150 MHz, CDCl3)
d 164.80, 159.49, 150.71, 149.02, 148.85,
142.07, 135.13, 134.37, 133.14, 125.41, 118.03, 117.45, 117.23, 116.74
(s), 113.18, 111.63, 110.81, 110.09, 109.93, 109.75, 39.50, 35.32; HRMS
4.5.16. Data for 14b
White solid; yield: 64%; mp 163e165 ꢁC; 1H NMR (400 MHz,
(MALDI): Calcd for
451.0850.
C
20H14F4N4O2S [MþH]þ 451.0852. Found:
DMSO-d6)
d
10.16 (s, 1H), 8.50 (s, 1H), 8.07 (s, 1H), 7.62 (d, J ¼ 8.8 Hz,
1H), 7.52 (d, J ¼ 8.8 Hz, 1H), 7.45 (d, J ¼ 8.4 Hz, 2H), 7.35 (t,
J ¼ 56.0 Hz, 1H), 6.90 (d, J ¼ 8.4 Hz, 2H), 4.57 (s, 2H), 3.98 (s, 3H),
4.6. Enzymatic kinetics [24e26]
3.73 (s, 3H); 13C NMR (150 MHz, CDCl3)
d 165.68, 159.57, 159.25,
148.80, 142.30, 134.99, 134.33, 130.33, 127.63, 117.06, 114.12, 111.60,
110.81, 109.73, 55.27, 39.55, 36.16; HRMS (MALDI): Calcd for
C
The preparation of succinate-cytochrome c reductase (SCR,
mixture of respiratory SQR and complex III) from porcine heart was
essentially as reported. The activity of SCR was measured by
21H18F2N4O3S [MþH]þ 445.1146. Found: 445.1145.