1022
Vol. 52, No. 8
Table 1. COX-Inhibitory Activity of Compounds (1—8)
for 1 h. After cooling, the whole was dissolved in dichloromethane, dried
with magnesium sulfate, and evaporated. The residue was recrystallized
from a mixed solvent of n-hexane and dichloromethane to afford the desired
compound as colorless crystals.
1: mp 195—198 °C; 1H-NMR (500 MHz, CDCl3) d: 7.97 (dd, Jꢀ5.6,
3.0 Hz, 2H), 7.80 (dd, Jꢀ5.6, 3.0 Hz, 2H), 7.52 (m, 2H), 7.44 (m, 3H); MS
(FAB, MꢁHꢁ) 244; Anal. Calcd for C14H9NO2: C, 75.33; H, 4.06; N, 6.27.
Found: C, 75.22; H, 4.16; N, 6.55.
% Inhibitiona)
3: mp 170—172 °C; 1H-NMR (500 MHz, CDCl3) d: 7.96 (dd, Jꢀ5.1,
3.0 Hz, 2H), 7.79 (dd, Jꢀ5.1, 3.0 Hz, 2H), 7.39 (t, Jꢀ7.7 Hz, 1H), 7.23 (m,
3H), 2.42 (s, 3H); MS FAB, MꢁHꢁ) 238; Anal. Calcd for C15H11NO2: C,
75.94; H, 4.67; N, 5.90. Found: C, 75.91; H, 4.76; N, 5.90.
Compd.
n
R
COX1
COX2
1
2
3
4
5
6
7
8
0
0
0
0
0
0
0
1
H
2-Me
3-Me
4-Me
2,6-diMe
3,5-diMe
2,3-diMe
2,3-diMe
12.1
12.1
9.29
9.70
19.0
17.2
24.0
19.7
9.70
30.6
77.2
39.0
4: mp 195—198 °C; 1H-NMR (500 MHz, CDCl3) d: 7.96 (dd, Jꢀ4.7,
3.0 Hz, 2H), 7.79 (dd, Jꢀ4.7, 3.0 Hz, 2H), 7.31 (m, 2H), 7.26 (m, 2H), 2.41
(s, 3H); MS (FAB, MꢁHꢁ) 238; Anal. Calcd for C15H11NO2: C, 75.94; H,
4.67; N, 5.90. Found: C, 75.67; H, 4.76; N, 5.90.
0.400
iab)
iab)
7: mp 165—168 °C; 1H-NMR (500 MHz, CDCl3) d: 7.96 (dd, Jꢀ4.7,
3.0 Hz, 2H), 7.80 (dd, Jꢀ4.7, 3.0 Hz, 2H), 7.24 (m, 2H), 7.05 (d, Jꢀ7.3 Hz,
1H), 2.36 (s, 3H), 2.08 (s, 3H); MS (FAB, MꢁHꢁ) 252; Anal. C16H13NO2:
C, 76.48; H, 5.21; N, 5.57. Found: C, 76.44; H, 5.45; N, 5.45.
iab)
72.6
52.0
Aspirin
Acknowledgements The work described in this paper was partially sup-
ported by a Grant-in-aid for Scientific Research from The Ministry of Edu-
cation, Culture, Sports, Science and Technology, Japan.
a) Compounds were screened for inhibitory activity on COX at the concen-
tration of 100 mM. b) ia: inactive at the concentration of 100 mM.
References
On the other hand, for the COX-2-inhibitory activity, the
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2-(Substituted phenyl)-1H-isoindole-1,3-dione (General Method)
A
mixture of phthalic anhydride and substituted aniline was heated at 160 °C