Browse > Article
http://dx.doi.org/10.5012/bkcs.2012.33.2.535

Synthesis and Biological Evaluation of N-(Aminopyridine) Benzamide Analogues as Histone Deacetylase Inhibitors  

Zhang, Qing-Wei (State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China Pharmaceutical Industry Research Institute)
Li, Jian-Qi (State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China Pharmaceutical Industry Research Institute)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.2, 2012 , pp. 535-540 More about this Journal
Abstract
A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.
Keywords
N-(Aminopyridine) benzamide; HDAC inhibition; Anticancer activity;
Citations & Related Records
 (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Zhou, N. Z.; Moradei, O.; Raeppel, S.; Leit, S.; Fréchette, S.; Gaudette, F.; Paquin, I.; Bernstein, N.; Bouchain, G.; Vaisburg, A.; Jin, Z.; Gillespie, J.; Wang, J. J.; Fournel, M.; Yan, P. T.; Trachy- Bourget, M.-C.; Kalita, A.; Lu, A.-H.; Rahil, J.; MacLeod, A. R.; Li, Z.; Besterman, J. M.; Delorme, D. J. Med. Chem. 2008, 51, 4072.   DOI   ScienceOn
2 Liu, L.; Chen, B.; Qin, S.; Li, S.; He, X.; Qiu, S.; Zhao, W.; Zhao, H. Biochem Biophys Res. Commun. 2010, 392, 190.   DOI   ScienceOn
3 Moradei, O.; Vaisburg, A.; Martell, R. E. Curr. Top. Med. Chem. 2008, 8, 841.   DOI   ScienceOn
4 Miller, T. A.; Witter, D. J.; Belvedere, S. J. J. Med. Chem. 2003, 46, 5097.   DOI   ScienceOn
5 Mitra, A. K.; De, A.; Karchaudhuri, N. Synthetic Commun. 1999, 29, 573.   DOI   ScienceOn
6 Marson, C. M.; Mahadevan, T.; Dines, J.; Segmany, S.; Morrell, J. M.; Alao, J. P.; Joel, S. P.; Vigushin, D. M.; Coombes, R. C. Bioorg. Med. Chem. Lett. 2007, 17, 136.   DOI   ScienceOn
7 Glaser, K. B. Biochem. Pharm. 2007, 74, 659.   DOI   ScienceOn
8 Rodriquez, M.; Aquino, M.; Bruno, I.; De Martino, G.; Taddei, M.; Gomez-Paloma, L. Curr. Med. Chem. 2006, 13, 1119.   DOI   ScienceOn
9 Dokmanovic, M.; Marks, P. A. J. Cell. Biochem. 2005, 96, 293.   DOI   ScienceOn
10 Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Nat. Rev. Drug Discov. 2006, 5, 769.   DOI   ScienceOn
11 Minucci, S.; Pelicci, P. G. Nat. Rev. Cancer 2006, 6, 38.   DOI   ScienceOn
12 Choi, J. H.; Kwon, H. J.; Yoon, B. I.; Kim, J. H.; Han, S. U.; Joo, H. J.; Kim, D. Y. Jpn. J. Cancer Res. 2001, 92, 1300.   DOI
13 Wilson, A. J.; Byun, D. S.; Popova, N.; Murray, L. B.; L'Italien, K.; Sowa, Y.; Arango, D.; Velcich, A.; Augenlicht, L. H.; Mariadason, J. M. J. Biol. Chem. 2006, 281, 13548.   DOI   ScienceOn
14 Glaser, K. B.; Li, J.; Staver, M. J.; Wei, R.-Q.; Albert, D. H.; Davidsen, S. K. Biochem. Biophys. Res. Commun. 2003, 310, 529.   DOI   ScienceOn
15 Altucci, L.; Rossin, A.; Raelsberger, W.; Reitmair, A.; Chomienne, C.; Gronemeyer, H. Nat. Med. 2001, 7, 680.   DOI   ScienceOn
16 Inoue, S.; Mai, A.; Dyer, M. J. S.; Cohen, G. M. Cancer Res. 2006, 66, 6785.   DOI   ScienceOn
17 Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, E. M.; Ferrara, F.; Bresciani, F.; Weisz, A.; de Lera, A. R.; Gronemeyer, H.; Altucci, L. Nat. Med. 2005, 11, 77.   DOI   ScienceOn
18 Karagiannis, T. C.; El-Osta, A. Leukemia 2007, 21, 61.   DOI   ScienceOn
19 Senese, S.; Zaragoza, K.; Minardi, S.; Muradore, I.; Ronzoni, S.; Passafaro, A.; Bernard, L.; Draetta, G.; Alcalay, M.; Seiser, C.; Chiocca, S. Mol. Cell. Biol. 2007, 27, 4784.   DOI   ScienceOn
20 Grant, S.; Easley, C.; Kirkpatrick, P. Nat. Rev. Drug Disc. 2007, 6, 21.   DOI   ScienceOn
21 Suzuki, T.; Ando, T.; Tsuchiya, K.; Fukazawa, N.; Saito, A.; Mariko, Y.; Yamashita, T.; Nakanishi, O. J. Med. Chem. 1999, 42, 3001.   DOI   ScienceOn
22 Marks, P. A.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Nat. Rev. Cancer 2001, 1, 194.   DOI   ScienceOn
23 Hassig, C. A.; Schreiber, S. L. Curr. Opin. Chem. Biol. 1997, 1,300.   DOI   ScienceOn
24 Kouzarides, T. Curr. Opin. Genet. Dev. 1999, 9, 40.   DOI   ScienceOn
25 Grunstein, M. Nature 1997, 389, 349.   DOI   ScienceOn
26 Cheung, W. L.; Briggs, S. D.; Allis, C. D. Curr. Opin. Cell Biol. 2000, 12, 326.   DOI   ScienceOn
27 Chunaram, C.; Chanchal, K.; Florian, G.; Michael, L. N.; Michael, R.; Tobias, C. W.; Jesper, V. O.; Matthias, M. Science 2009, 325, 834.   DOI   ScienceOn