X.J. Liu et al. / Chinese Chemical Letters 22 (2011) 1139–1142
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Table 1
Melting points, yields and MS and 1H NMR data of the novel compounds.
Compd.
Mp (8C)
Yield (%)
36
MS (m/z)
1H NMR, d, J (Hz)
2d
199–200
505
(400 MHz, CDCl3): 4.20 (s, 3H), 7.02 (s, 2H), 7.22 (t, 1H, J = 8.8),
7.36 (d, 1H, J = 8.0), 7.40 (s, 1H), 7.59 (d, 2H, J = 8.0), 8.24 (d, 1H, J = 8.8),
8.50 (d, 1H, J = 4.4), 8.54 (s, 1H), 8.66 (d, 1H, J = 8.4), 8.87 (s, 1H), 10.43 (s, 1H)
(400 MHz, CDCl3): 4.22 (s, 3H), 5.90 (t, 2H, J = 14.4), 7.25 (t, 1H, J = 8.0),
7.40(t, 2H, J = 15.6), 7.83 (d, 1H, J = 8.4), 7.87 (s, 1H), 8.26(d, 2H, J = 7.2),
8.40 (d, 1H, J = 8.8), 8.48(d, 1H, J = 8.0), 8.94 (s, 1H), 10.12 (s, 1H)
(400 MHz, CDCl3): 3.85 (d, 3H, J = 2.8), 3.93 (s, 3H), 3.97 (s, 3H), 4.16 (s, 3H),
5.32 (s, 3H), 6.54 (d, 4H, J = 6.4), 6.56 (s, 3H), 7.18 (d, 3H, J = 8.8),
8.25 (q, 2H, J = 10.0), 8.44 (d, 1H, J = 9.6), 8.53 (s, 1H), 8.55 (s, 1H),
8.76 (d, 1H, J = 2.0), 10.39 (s, 1H)
2e
228–229
188–189
30
35
600
467
2k
2l
219–222
40
467
(400 MHz, CDCl3): 3.84 (d, 3H, J = 2.8), 3.87 (s, 3H), 3.93 (s, 3H),
3.97 (s, 3H),4.18 (s, 3H), 6.65 (d, 2H, J = 8.4), 6.87 (t, 2H, J = 16), 20 (d, 1H, J = 9.2),
8.26 (t, 2H, J = 10.8), 8.41 (d, 1H, J = 2.4), 8.68 (s, 1H), 8.79 (d, 1H, J = 2.0),
10.62 (s, 1H)
2o
2p
2q
3a
282–283
254–255
>300
36
50
52
75
501
501
501
419
(400 MHz, DMSO-d6): 4.15 (s, 3H), 7.64 (m, 2H, J = 104), 8.05 (m, 2H, J = 15.2),
8.15 (d, 1H, J = 2.8), 8.17 (d, 1H, J = 2.8), 8.22 (d, 1H, J = 2.8), 8.38 (d, 1H, J = 7.2),
8.61(m, 1H, J = 26), 8,92 (s, 1H), 8.94 (s, 1H)
(400 MHz, DMSO-d6): 4.14 (s, 3H), 7.51 (m, 3H, J = 11.6), 7.61 (m, 1H, J = 11.2),
7.76 (m, 2H, J = 16.0), 8.22 (dd, 1H, J = 10.4), 8.44 (d, 1H, J = 12.0),
8.69 (d, 1H, J = 12.0), 10.31 (s, 1H), 10.55 (s, 1H)
(400 MHz, DMSO-d6): 4.12 (s, 3H), 7.29 (t, 2H, J = 14.4), 7.42 (d, 1H, J = 10.8),
7.64 (m, 2H, J = 11.6), 8.18 (dd, 1H, J = 15.2), 8.54 (d, 2H, J = 6.0), 8.62 (d, 1H, J = 2.0),
10.40 (s, 1H), 10.63 (s, 1H)
210–212
(300 MHz, DMSO-d6): 3.90 (s,3H), 7.18 (d, 2H, J = 6.6), 7.30 (t, 2H, J = 6.6),
7.46 (d, 1H, J = 0.3), 7.60 (d, 2H, J = 10.2), 7.95 (d, 2H, J = 1.2), 7.97 (t, 1H, J = 1.2),
8.32 (t, 1H, J = 3.0), 10.92 (s, 1H), 10.93 (s, 1H)
3b
3c
3e
206–207
204–206
198–200
87
38
67
456
489
480
(300 MHz, CDCl3): 4.04 (s, 3H), 6.59 (s, 1 H), 7.01 (q, 3H), 7.10 (m, 5H, J = 21.0),
7.51 (s, 1H), 7.84 (d, 1H, J = 8.7), 8.22 (d, 1H, J = 2.4), 7.51 (s, 1H)
(300 MHz, DMSO-d6): 3.89 (s, 3H), 7.14 (t, 3H, J = 6.6), 7.30 (q, 5H, J = 20.1),
7.41 (d, 1H, J = 8.7), 7.80 (d, 1H, J = 8.6), 7.95 (d, 1H, J = 8.8), 9.94 (s, 1H), 10.06 (s, 1H)
(300 MHz, CDCl3): 3.62 (s, 3H), 3.72 (s, 3H), 3.96 (s, 3H), 6.69 (s, 1H),
6.71 (t, 1H, J = 9.9), 6.75 (s, 2H), 6.85 (d, 1H, J = 6.0), 6.87 (s, 1H), 6.90 (s, 1H),
6.98 (t, 2H, J = 6.0), 7.26 (s, 1H), 7.43 (t, 1H, J = 3.9), 7.50 (s, 1H), 8.30 (d, 1H, J = 2.1)
(300 MHz, DMSO-d6): 3.90 (s, 3H), 3.90 (s, 2H), 3.99 (s, 2H), 6.57 (d, 1H, J = 1.0),
6.83–7.29 (m, 18H), 7.77 (d, 1H, J = 7.2), 7.95 (s, 1H), 9.68 (s, 1H), 9.70 (s, 1H)
(300 MHz, DMSO-d6): 4.17 (s, 3H), 4.01 (s, 2H), 4.14 (s, 2H), 5.58 (d, 1H, J = 7.8),
7.00 (d, 1H, J = 7.8), 7.13 (d, 1H, J = 7.2), 7.26 (s, 1H), 7.35 (d, 2H, J = 7.8), 7.45
(d, 1H, J = 7.5), 7.80 (d, 1H, J = 9.0), 7.97 (s, 1H), 8.68 (s, 1H), 8.75 (s, 1H)
(400 MHz, CDCl3): 3.50 (s, 3H), 3.61 (s, 3H), 3.78 (d, 6H, J = 2.4), 4.01 (s, 3H),
6.52 (t, 1H, J = 23.6), 6.44 (q, 2H, J = 18.4), 6.64 (s, 1H), 6.90 (d, 1H, J = 8.8),
7.22 (s, 1H), 7.38 (d, 2H, J = 8.8), 7.76 (d, 1H, J = 8.8), 8.22 (s, 1H)
(400 MHz, CDCl3): 3.60 (s, 3H), 3.70 (s, 3H), 3.73 (s, 3H), 3.76 (s, 3H), 3.99 (s, 3H),
6.52 (q, 1H, J = 10.8), 6.59 (s, 1H), 6.62 (s, 1H), 6.65 (d, 2H, J = 9.6), 6.69 (s, 1H),
6,91 (d, 1H, J = 10.8), 7.02 (s, 1H), 7.54 (s, 1H), 786 (d, 1H, J = 8.8), 8.35 (s, 1H)
3f
247–248
191–192
73
61
599
497
3g
3h
3i
162–163
177–178
42
50
537
538
The melting points were determined but the thermometer was uncorrected; 1H NMR were recorded in DMSO-d6 or CDCl3 on a Bruker ARX-300 or
400 MHz spectrometer; chemical shifts are recorded in d relative to TMS as internal standard; mass spectral datd were obtained on Agilent 6310.
3. Results
A total of 27 target compounds were synthesized. The results in vitro on platelet using Born’s test method on mice in
Table 2 showed that three compounds 2e, 2i and 3g exhibited significant activities on antiplatelet aggregation, more
than picotamide and aspirin, and eight compounds 2d, 2j, 2k, 2l, 2q, 2r, 3f and 3i only superior to picotamide, while
compounds 2a, 2d and 3b are comparable with picotamide. The rest of the compounds were less active than the two
drugs. The inhibitory rates of 10 compounds (2c, 2f, 2g, 2h, 2m, 2n, 3a, 3c, 3d, 3e) are lower than 5.0%. The
preliminary SAR shows that it is favorite for the 2 series to increase the activities via steric hindrance groups, such as I