904
Y.J. Yang et al. / Chinese Chemical Letters 21 (2010) 902–904
derivative 9 showed potent activity against all cell lines with IC50 values ranging from 5.841 to 10.014 mg/mL. Furan
derivative 4 and thiazole derivative 15 displayed similar activity to derivative 9, but lost activity against A549 and
BGC-823 cell lines (IC50 >10 mg/mL), respectively. Others were inactive (IC50 >10 mg/mL). Thus activity was
strongly influenced by the nature of heterocyclic rings. After comparison of 15 and 16 which share the same
heterocycle, the modification at 3-position in the thiazoline ring gave an indication towards the design of new and
potentially more active compounds. Additional effects will be devoted to study the influence of the chain between the
phthalimide and heterocyclic rings.
In summary, we reported a series of phthalimide derivatives with various heterocyclic rings [17]. Their cytotoxic
activity was evaluated against five human cancer cell lines in vitro. In addition, all of the reactions described herein
were highly effective under mild conditions. A large number of structurally diverse phthalimide derivatives for drug
development projects can be rapidly synthesized in good purity and high yield using this method. Further synthesis and
biological evaluation of phthalimide derivatives are in progress.
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[17] Selected spectral data. 4—MS (EI, m/z): [M+H]+ 342; 1H NMR (300 MHz, CDCl3): d 2.03 (d, 3H, J = 7.5 Hz), 5.88 (q, 1H, J = 7.5 Hz), 7.43–
7.71 (m, 6H), 7.78–7.87 (m, 3H), 7.97 (d, 1H, J = 9.0 Hz), 8.28 (d, 1H, J = 8.1 Hz); 5—MS (ESI, m/z): [M+H]+ 424.2; 1H NMR (300 MHz,
CDCl3): d 1.85 (d, 3H, J = 7.2 Hz), 3.82 (s, 3H), 3.87 (s, 3H), 3.99 (s, 3H), 5.61 (q, 1H, J = 7 .2 Hz), 6.60 (s, 1H), 7.69–7.72 (m, 2H), 7.83–7.86
(m, 2H); 6—MS (ESI, m/z): [M+H]+ 292.2; 1H NMR (300 MHz, CDCl3): d 1.96 (d, 3H, J = 6.9 Hz), 5.79 (q, 1H, J = 6.9 Hz), 6.75–6.80 (m,
1H), 7.13–7.18 (m, 1H), 7.56–7.62 (m, 2H), 7.69–7.71 (m, 2H), 7.82–7.84 (m, 2H), 8.06–8.08 (m, 1H); 8—MS (ESI, m/z): [M+H]+ 389.1; 1H
NMR (300 MHz, CDCl3): d 1.71 (d, 3H, J = 6.6 Hz), 3.45 (dd, 2H, J = 21.9 Hz), 5.22(q, 1H, J = 6.6 Hz), 7.13–7.17 (m, 2H), 7.24–7.29 (m,
1H), 7.63–7.69 (m, 4H), 7.77–7.80 (m, 2H); 9—MS (ESI, m/z): [M+H]+ 457.1; 1H NMR (300 MHz, DMSO-d6): d 1.81(d, 3H, J = 7.2 Hz), 2.13
(s, 3H), 2.15 (s, 3H), 2.19 (s, 3H), 2.68 (s, 3H), 5.36 (q, 1H, J = 7.2 Hz), 7.86–7.87 (m, 4H); 10—MS (ESI, m/z): [M+H]+ 390.1; 1H NMR
(300 MHz, DMSO-d6): d 1.76 (d, 3H, J = 7.2 Hz), 4.03 (dd, 2H, J = 18.3 Hz), 5.41 (q, 1H, J = 7.2 Hz), 7.31–7.45 (m, 3H), 7.84–7.94 (m, 6H);
11—MS (ESI, m/z): [M+H]+ 274.1; 1H NMR (300 MHz, DMSO-d6): d 1.69 (d, 3H, J = 7.5 Hz), 5.17 (q, 1H, J = 7.5 Hz), 6.39 (s, 1H), 6.87 (s,
2H), 7.83 (s, 4H); 12–MS (ESI, m/z): [M+H]+ 350.1; 1H NMR (300 MHz, DMSO-d6): d 1.80 (d, 3H, J = 7.5 Hz), 5.33 (q, 1H, J = 7.5 Hz), 6.74
(m, 1H), 6.78–6.83 (m, 1H), 7.01–7.06 (m, 1H), 7.35–7.37 (m, 1H), 7.82–7.91 (m, 4H), 10.10 (s, 1H); 13–MS (ESI, m/z): [M+H]+ 304.1; 1H
NMR (300 MHz, DMSO-d6): d 1.72 (d, 3H, J = 8.4 Hz), 2.10 (s, 3H), 5.27 (q, 1H, J = 8.4 Hz), 6.50 (s, 1H), 7.60–7.63 (m, 2H), 7.70–7.71 (m,
2H), 8.33 (s, 1H); 14–MS (ESI, m/z): [M+H]+ 331.1; 1H NMR (300 MHz, DMSO-d6): d 1.74 (d, 3H, J = 6.9 Hz), 5.25 (q, 1H, J = 6.9 Hz), 6.67
(m, 1H), 7.46–7.51 (m, 2H), 7.55–7.62 (m, 1H), 7.80–7.89 (m, 6H), 9.47 (s, 1H), 10.73 (s, 1H); 15–MS (ESI, m/z): [M+H]+ 364.1; 1H NMR
(300 MHz, DMSO-d6): d 1.69 (d, 3H, J = 7.2 Hz), 3.23 (s, 3H), 5.37 (q, 1H, J = 7.2 Hz), 6.34 (s, 1H), 6.89–6.98 (m, 3H), 7.25–7.30 (m, 2H),
7.83–7.89 (m, 4H); 16–MS (ESI, m/z): [M+H]+ 426.1; 1H NMR (300 MHz, DMSO-d6): d 1.55 (d, 3H, J = 6.9 Hz), 5.39 (q, 1H, J = 6.9 Hz),
6.49 (s, 1H), 6.79–6.98 (m, 5H), 7.15–7.27 (m, 3H), 7.44 (m, 2H), 7.67–7.71 (m, 2H), 7.75–7.83 (m, 2H); 17–MS (ESI, m/z): [M+H]+ 377.1; 1H
NMR (300 MHz, DMSO-d6): d 1.76 (d, 3H, J = 7.2 Hz), 5.29 (q, 1H, J = 7.2 Hz), 6.76 (s, 1H), 7.34–7.41 (m, 3H), 7.57–7.60 (m, 2H), 7.85–
7.88 (m, 5H), 11.99 (s, 1H); 18–MS (ESI, m/z): [M+H]+ 378.1; 1H NMR (300 MHz, DMSO-d6): d 1.76 (d, 3H, J = 7.2 Hz), 5.30 (q, 1H,
J = 7.2 Hz), 6.82 (s, 1H), 7.31–7.34 (m, 1H), 7.80–7.90 (m, 7H), 8.51 (d, 1H, J = 5.1 Hz), 12.24 (s, 1H).