T. Ikeda et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5978–5981
5981
13. Compound 6: white powder, 1H NMR (400 MHz, DMSO-d6) d: 1.68–1.88 (3H,
m), 2.22–2.45 (3H, m), 3.21–3.31(1H, m), 3.50 (1H, d, J = 15.0 Hz), 3.93 (3H, s),
3.99 (3H, s), 4.43 (1H, d, J = 15.0 Hz), 4.84–4.95 (1H, m), 5.14 (1H, br s), 7.04
(1H, dd, J = 1.5, 9.0 Hz), 7.19 (1H, s), 7.91 (1H, d, J = 1.5 Hz), 7.91 (1H, s), 8.30
(1H, d, J = 9.0 Hz), 9.60 (1H, br s); HRMS (ESI) calcd for C22H24NO4 [M+H]+,
(3H, s), 4.60 (1H, d, J = 15.5 Hz), 7.24 (1H, s), 7.53–7.64 (2H, m), 7.97–8.04 (1H,
m), 8.16 (1H, s), 8.72–8.78(1H, m); HRMS (ESI) calcd for C20H24NO2 [M+H]+,
334.1807. Found: 334.1816; ½a D27
ꢂ
+109.16 (c = 0.05, CHCl3).
Compound 14: yellow powder, 1H NMR (400 MHz, DMSO-d6) d: 1.53–1.70 (1H,
m), 1.75–1.94 (2H, m), 2.07–2.23 (1H, m), 2.31–2.44 (2H, m), 2.71–2.83 (1H,
m), 3.26–3.42 (2H, m), 3.54 (1H, d, J = 15.4 Hz), 3.94 (3H, s), 4.00 (3H, s), 4.58
(1H, d, J = 15.4 Hz), 7.23 (1H, s), 7.43 (1H, ddd, J = 2.7, 8.8, 11.5 Hz), 8.05 (1H,
dd, J = 6.1, 8.8 Hz), 8.11 (1H, s), 8.59 (1H, dd, J = 2.7, 11.5 Hz); HRMS (ESI) calcd
366.1705. Found: 366.1713; ½a D26
ꢂ
+96.52 (c = 0.05, CHCl3/CH3OH = 1:1).
Compound 8: white powder, 1H NMR (400 MHz, DMSO-d6) d: 1.52–1.68 (1H,
m), 1.75–1.94 (2H, m), 2.07–2.23 (1H, m), 2.26–2.44 (2H, m), 2.71–2.83 (1H,
m), 3.26–3.42 (2H, m), 3.50 (1H, d, J = 15.0 Hz), 3.92(3H, s), 3.98 (3H, s), 4.53
(1H, d, J = 15.0 Hz), 7.09 (1H, dd, J = 2.3, 8.9 Hz), 7.18 (1H, s), 7.83 (1H, d,
J = 8.9 Hz), 7.92(1H, s), 7.94 (1H, d, J = 2.3 Hz); HRMS (ESI) calcd for C22H24NO3
for C22H22NO2F [M+H]+, 352.1713. Found: 352.1645; ½a 2D7
ꢂ
+120.78 (c = 0.10,
CHCl3).
14. Some compounds exhibited selective cytotoxicities against the A549 and
HCT116 cell lines. The reason for this finding remains unknown at this time.
15. After transplanting HCT116 cells (2 ꢀ 106 cells/mouse) subcutaneously into
6 week old male nude mice, the mice were grouped (5 mice/group) on the day
when the estimated tumor volume calculated by the following formula (A)
reached about 100 mm3 (Day 0). Samples were administered intraperitoneally
10 times on days 1–5 & 8–12. Tumors were excised and weighed on day 21
after tumor inoculation. The inhibition rate (%) was calculated using the
following formula: [1 ꢁ (mean tumor weight of tested mice)/(mean tumor
weight of control mice] ꢀ 100.
[M+H]+, 350.1756. Found: 350.1761;
CH3OH = 1:1).
½
a 2D6
ꢂ
+102.99 (c = 0.11, CHCl3/
Compound 11: white powder, 1H NMR (400 MHz, DMSO-d6) d: 1.58–1.70 (1H,
m), 1.75–1.94 (2H, m), 2.07–2.23 (1H, m), 2.31–2.44 (2H, m), 2.35 (3H, s), 2.81
(1H, dd, J = 11.2, 15.4), 3.27–3.42 (2H, m), 3.56 (1H, d, J = 15.3 Hz), 3.94 (3H, s),
4.00 (3H, s), 4.60 (1H, d, J = 15.3 Hz), 7.24 (1H, s), 7.35 (1H, dd, J = 1.0, 9.0 Hz),
8.03 (1H, d, J = 9.0 Hz), 8.07 (1H, s), 8.49 (1H, s); HRMS (ESI) calcd for
C
24H26NO4 [M+H]+, 392.1862. Found: 392.1875; ½a 2D9
ꢂ
+112.42 (c = 0.05, CHCl3).
Compound 13: yellow powder, 1H NMR (400 MHz, DMSO-d6) d: 1.58–1.70 (1H,
m), 1.75–1.94 (2H, m), 2.07–2.23 (1H, m), 2.31–2.44 (2H, m), 2.81 (1H, dd,
J = 10.5, 15.9 Hz), 3.26–3.44 (2H, m), 3.57 (1H, d, J = 15.5 Hz), 3.94 (3H, s), 4.00
Estimated tumor volume = 1/2 ꢀ long diameter ꢀ short diameter ꢀ short
diameter (A).