S.P. Chen et al. / Chinese Chemical Letters 22 (2011) 1033–1035
1035
Table 1
Inhibition effect of compounds 7 and 8 toward EGFR in vitro.
Compounds
Concentration (mmol/L)
Inhibition (%)
7
5.3
5.5
2.2
44.4
86.1
8
Gefitinib
10.0
In conclusion, a novel quinazoline dimer was designed and synthesized with good water solubility. The quinazoline
dimer 8 showed moderate inhibition against EGFR in vitro and its further bioactivity evaluation is in progress in our
laboratory. A facile method was developed for the construction of quinazoline dimers and hoped to be useful in the
synthesis of other dimers connected by a carbon–carbon bond.
Acknowledgments
We are grateful for the financial support of Key International S&T Cooperation Projects (No. 2008DFA31040 and
No. 2009DFA32080) of Ministry of Science and Technology of the People’s Republic of China. We are also grateful to
the Shanghai Institute of Materia Medica Chinese Academy of Sciences for the continuous support in doing biological
assay.
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[17] Spectral data. Compound 7 HRMS(ESI): calcd. for C60H63N6O22Cl2+ 1289.3372, found 1289.3395; 1H NMR (600 MHz, CDCl3): d 8.71 (s,
1H, ArH), 8.22 (s, 1H, ArH), 8.15 (s, 1H, ArH), 7.82 (s, 1H, ArH), 7.58–7.57 (d, 2H, J = 7.7 Hz, ArH), 6.93–6.91 (d, 2H, J = 8.8 Hz, ArH),
5.26–5.23 (t, 1H, J = 9.6 Hz), 5.12–5.09 (t, 1H, J = 9.6 Hz), 5.05–5.02 (dd, 1H, J = 9.3, 7.7 Hz), 4.69–4.68 (d, 1H, J = 8.2 Hz), 4.28–4.25 (dd,
1H, J = 12.1, 4.4 Hz), 4.15–4.12 (m, 4H), 3.96–3.94 (m, 1H), 3.75–3.73 (m, 1H), 2.09 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.00 (s, 3H, OAc), 1.98
(s, 3H, OAc). 13C NMR (150 MHz, CDCl3): d 170.9, 170.4, 169.7, 169.5, 157.4, 156.3, 155.9, 142.1, 131.2, 131.0, 130.6, 125.1, 124.8, 124.7,
122.1, 116.0, 115.2, 115.1, 101.1, 72.8, 72.0, 71.3, 68.5, 68.4, 67.6, 62.0, 20.9, 20.8, 20.7, 20.6. Compound 8 HRMS(ESI): calcd. for
C
44H47N6O14Cl2+ 953.2527, found 953.2505; 1H NMR (600 MHz, DMSO-d6): d 9.96 (s, 1H, NH), 8.90 (s, 1H, ArH), 8.61 (s, 1H, ArH), 7.85 (s,
1H, ArH), 7.75–7.73 (d, 2H, J = 8.8 Hz, ArH), 7.04–7.03 (d, 2H, J = 9.4 Hz, ArH), 5.09 (s, 1H), 4.96 (s, 1H), 4.56 (s, 1H), 4.27–4.26 (d, 1H,
J = 7.7 Hz), 4.20–4.17 (m, 2H), 4.14–4.11 (m, 1H), 3.87–3.84 (m, 1H), 3.71–3.69 (d, 1H, J = 11.0 Hz), 3.49–3.46 (m, 1H), 3.19–3.15 (m, 3H),
3.10–3.08 (d, 1H, J = 9.4 Hz), 3.03–3.00 (t, 1H, J = 9.4 Hz). 13C NMR (150 MHz, DMSO-d6): d 157.6, 156.2, 155.8, 148.9, 142.0, 132.3,
130.6, 130.2, 124.9, 124.8, 124.0, 116.4, 115.0, 114.9, 103.7, 77.5, 77.3, 74.0, 70.6, 68.0, 67.7, 61.7.