7162
P. Zhan et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7155–7162
19. Zhan, P.; Liu, X.; Zhu, J.; Fang, Z.; Li, Z.; Pannecouque, C.; De Clercq, E. Bioorg.
Acknowledgments
Med. Chem. Lett. 2009, 17, 5775.
20. Zhan, P.; Liu, X.; Fang, Z.; Pannecouque, C.; De Clercq, E. Bioorg. Med. Chem. Lett.
2009, 17, 6374.
21. Zhan, P.; Liu, H.; Liu, X.; Wang, Y.; Pannecouque, C.; Witvrouw, M.; De Clercq, E.
Med. Chem. Res. 2009, 19, 652.
22. Zhan, P.; Chen, X.; Li, X.; Li, D.; Tian, Y.; Chen, W.; Pannecouque, C.; De Clercq,
E.; Liu, X. Eur. J. Med. Chem. 2011, 46, 5039.
23. Zhan, P.; Wang, L.; Liu, H.; Chen, X.; Li, X.; Jiang, X.; Zhang, Q.; Liu, X.;
Pannecouque, C.; Naesens, L.; De Clercq, E.; Liu, A.; Du, G. Arch. Pharmacol. Res.
2012, 1037, 35.
24. (a) Patani, G. A.; LaVoie, E. J. Chem. Rev. 1996, 96, 3147; (b) Olesen, P. H. Curr.
Opin. Drug Discov. Devel. 2001, 4, 471; (c) Lima, L. M.; Barreiro, E. J. Curr. Med.
Chem. 2005, 12, 23.
25. Fitt, J. J.; Gschwend, H. W. J. Org. Chem. 1977, 42, 2639.
26. Taylor, E. C.; Macor, J. E. J. Heterocycl. Chem. 1985, 22, 409.
27. Baraldi, P. G.; Preti, D.; Tabrizi, M. A.; Fruttarolo, F.; Saponaro, G.; Baraldi, S.;
Romagnoli, R.; Moorman, A. R.; Gessi, S.; Varani, K.; Andrea Borea, P. Bioorg.
Med. Chem. Lett. 2007, 15, 2514.
28. Suzuki, T.; Moriya, M.; Sakamoto, T.; Suga, T.; Kishino, H.; Takahashi, H.;
Ishikawa, M.; Nagai, K.; Imai, Y.; Sekino, E.; Ito, M.; Iwaasa, H.; Ishihara, A.;
Tokita, S.; Kanatani, A.; Sato, N.; Fukami, T. Bioorg. Med. Chem. Lett. 2009, 19,
3072.
The financial support from the National Natural Science
Foundation of China (NSFC No.81102320, No.30873133,
No.30772629, No.30371686), Key Project of NSFC for International
Cooperation (No.30910103908), Research Fund for the Doctoral
Program of Higher Education of China (No.20110131130005,
20110131120037), Independent Innovation Foundation of Shandong
University (IIFSDU, No.2010GN044), Shandong Postdoctoral Innova-
tion Science Research Special Program (No.201002023), China
Postdoctoral Science Foundation funded project (No.20100481282,
2012T50584) and KU Leuven (GOA 10/014) is gratefully
acknowledged.
We thank K. Erven, K. Uyttersprot and C. Heens for technical
assistance with the anti-HIV assays.
References and notes
29. Representative characterization data: 8a2: white solid, yield: 71.4%. mp: 101–
103 °C. 1H-NMR (600 MHz, DMSO-d6, ppm) d: 9.90 (s, 1H, NH), 9.70 (s, 1H,
CH@N), 7.75 (d, 1H, J = 7.8 Hz, PhH), 7.71 (d, 1H, J = 7.8 Hz), 7.66–7.62 (m, 2H),
7.58 (t, 1H, J = 7.2 Hz), 7.49 (d, 1H, J = 7.8 Hz), 7.33 (t, 1H, J = 7.8 Hz), 7.19 (t, 1H,
J = 7.2 Hz, Ph’H), 4.38 (s, 2H, CH2-S). 13C NMR (150 MHz, DMSO-d6, ppm): 166.5
(C@O), 161.8, 156.4, 154.4, 135.3, 133.0, 131.9, 131.0, 130.6, 130.2, 128.5,
1. Zhan, P.; Liu, X.; Li, Z. Curr. Med. Chem. 2009, 16, 2876.
2. Zhan, P.; Liu, X.; Li, Z.; Pannecouque, C.; De Clercq, E. Curr. Med. Chem. 2009, 16,
3903.
3. Zhan, P.; Chen, X.; Li, D.; Fang, Z.; De Clercq, E.; Liu, X. Med. Res. Rev. 2011.
4. Zhan, P.; Liu, X. Expert Opin. Ther. Pat. 2011, 5, 717.
128.2, 127.0, 126.6, 126.2, 35.2 (CH2-S). IR (KBr, cmÀ1): 3258 (
1689 ( C@O), 1592, 1525, 1468, 1441, 1311, 1235, 1143, 762 (
t
t
NH), 3066, 2929,
C–Cl), 750 ( C–S).
5. Zhan, P.; Li, Z.; Liu, X.; De Clercq, E. Mini. Rev. Med. Chem. 2009, 1014, 9.
6. Wang, Z.; Wu, B.; Kuhen, K. L.; Bursulaya, B.; Nguyen, T. N.; Nguyen, D. G.; He,
Y. Bioorg. Med. Chem. Lett. 2006, 16, 4174.
7. De La Rosa, M.; Kim, H. W.; Gunic, E.; Jenket, C.; Boyle, U.; Koh, Y. H.; Korboukh,
I.; Allan, M.; Zhang, W.; Chen, H.; Xu, W.; Nilar, S.; Yao, N.; Hamatake, R.; Lang,
S. A.; Hong, Z.; Zhang, Z.; Girardet, J. L. Bioorg. Med. Chem. Lett. 2006, 16, 4444.
8. Muraglia, E.; Kinzel, O. D.; Laufer, R.; Miller, M. D.; Moyer, G.; Munshi, V.;
Orvieto, F.; Palumbi, M. C.; Pescatore, G.; Rowley, M.; Williams, P. D.; Summa,
V. Bioorg. Med. Chem. Lett. 2006, 16, 2748.
t
t
C
17H12Cl2N4OS (Exact Mass: 390.01). 8a4: white solid, yield: 68.3%. mp: 99–
102 °C. 1H NMR (600 MHz, DMSO-d6, ppm) d: 9.83 (s, 1H, NH), 9.70 (s, 1H,
CH@N), 7.71 (d, 1H, J = 8.4 Hz, PhH), 7.66–7.62 (m, 4H), 7.58 (t, 1H, J = 7.8 Hz),
7.37 (t, 1H, J = 7.8 Hz), 7.14 (t, 1H, J = 7.2 Hz, Ph’H), 4.36 (s, 2H, CH2-S). 13C NMR
(150 MHz, DMSO-d6, ppm): 166.5 (C@O), 161.7, 156.4, 154.3, 136.6, 133.4,
133.3, 133.0, 131.9, 131.0, 130.7, 128.8, 128.5, 127.7, 127.0, 117.9, 35.2 (CH2-S).
IR (KBr, cmÀ1): 3336 (
1233, 1024, 756
17H12BrClN4OS (Exact Mass: 433.96). 8b15: grey solid, yield: 66.4%. mp:
t
NH), 3062, 1688 (
tC–S). MS (ESI): m/z 435.3 (M+1), 437.2 (M+3).
tC@O), 1594, 1526, 1437 (tN@N), 1311,
(
9. O’Meara, J. A.; Jakalian, A.; LaPlante, S.; Bonneau, P. R.; Coulombe, R.; Faucher,
A. M.; Guse, I.; Landry, S.; Racine, J.; Simoneau, B.; Thavonekham, B.; Yoakim, C.
Bioorg. Med. Chem. Lett. 2007, 17, 3362.
C
197–199 °C. 1H-NMR (400 MHz, DMSO-d6, ppm) d: 9.95 (s, 1H, SO2NH2), 9.75
(s, 1H, SO2NH2), 8.18 (d, 1H, J = 7.8 Hz, NH), 8.09 (d, 1H, J = 8.2 Hz, CH@N), 8.04
(d, 1H, J = 1.96 Hz, PhH), 7.90 (d, 1H, J = 8.5 Hz, PhH), 7.80–7.45 (m, 8H), 4.33 (s,
2H, CH2-S). 13C NMR (100 MHz, DMSO-d6, ppm): 166.8 (C@O), 161.9, 157.6,
154.2, 142.0, 139.4, 133.7, 131.6, 131.4, 130.4, 130.0, 129.1, 127.8, 127.8, 127.2,
126.0, 125.9, 125.7, 125.0, 116.4, 35.2 (CH2-S). MS (ESI): m/z 530.2 (M+1), 532.2
(M+3). C21H16BrN5O3S2 (Exact Mass: 528.99).
10. Gagnon, A.; Amad, M. H.; Bonneau, P. R.; Coulombe, R.; DeRoy, P. L.; Doyon, L.;
Duan, J.; Garneau, M.; Guse, I.; Jakalian, A.; Jolicoeur, E.; Landry, S.; Malenfant,
E.; Simoneau, B.; Yoakim, C. Bioorg. Med. Chem. Lett. 2007, 17, 4437.
11. Gagnon, A.; Landry, S.; Coulombe, R.; Jakalian, A.; Guse, I.; Thavonekham, B.;
Bonneau, P. R.; Yoakim, C.; Simoneau, B. Bioorg. Med. Chem. Lett. 2009, 19, 1199.
12. Moyle, G.; Boffito, M.; Stoehr, A.; Rieger, A.; Shen, Z.; Manhard, K.; Sheedy, B.;
Hingorani, V.; Raney, A.; Nguyen, M.; Nguyen, T.; Ong, V.; Yeh, L. T.; Quart, B.
Antimicrob. Agents Chemother. 2010, 54, 3170.
13. Li, D.; Zhan, P.; De Clercq, E.; Liu, X. J. Med. Chem. 2012, 55, 3595.
14. Zhao, H.; Guo, Z. Drug Discovery Today 2009, 14, 516.
15. Zhan, P.; Liu, X.; Cao, Y.; Wang, Y.; Pannecouque, C.; De Clercq, E. Bioorg. Med.
Chem. Lett. 2008, 18, 5368.
16. Zhan, P.; Liu, X.; Li, Z.; Fang, Z.; Li, Z.; Wang, D.; Pannecouque, C.; De Clercq, E.
Bioorg. Med. Chem. Lett. 2009, 17, 5920.
17. Zhan, P.; Liu, X.; Fang, Z.; Li, Z.; Pannecouque, C.; De Clercq, E. Eur. J. Med. Chem.
2009, 44, 4648.
18. Zhan, P.; Liu, X.; Li, Z.; Fang, Z.; Pannecouque, C.; De Clercq, E. Chem. Biodivers.
2010, 7, 1717.
30. Popovic, M.; Sarngadharan, M. G.; Read, E.; Gallo, R. C. Science 1984, 224, 497.
31. Barré-Sinoussi, F.; Chermann, J. C.; Rey, F.; Nugeyre, M. T.; Chamaret, S.; Gruest,
J.; Dauguet, C.; Axler-Blin, C.; Vézinet-Brun, F.; Rouzioux, C.; Rozenbaum, W.;
Montagnier, L. Science 1983, 220, 868.
32. Miyoshi, I.; Taguchi, H.; Kobonishi, I.; Yoshimoto, S.; Ohtsuki, Y.; Shiraishi, Y.;
Agaki, T. Gann Monogr. 1982, 28, 219.
33. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.;
Desmyter, J.; De Clercq, E. J. Virol. Methods 1988, 20, 309.
34. Pannecouque, C.; Daelemans, D.; De Clercq, E. Nat. Protoco. 2008, 3, 427.
35. (a) Suzuki, K.; Craddock, B. P.; Okamoto, N.; Kano, T.; Steigbigel, R. T. J. Virol.
Methods 1993, 44, 189–198; (b) Wu, J.; Liu, X.; Cheng, X.; Cao, Y.; Wang, D.; Li, Z.;
Xu, W.; Pannecouque, C.; Witvrouw, M.; De Clercq, E. Molecules 2003, 2007, 12.