Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2011.10.19
  • Accepted : 2011.12.08
  • Published : 2012.02.20
Download PDF
⟨ Previous Next ⟩

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

References

  1. Marks, P. A.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Nat. Rev. Cancer 2001, 1, 194. https://doi.org/10.1038/35106079
  2. Hassig, C. A.; Schreiber, S. L. Curr. Opin. Chem. Biol. 1997, 1,300. https://doi.org/10.1016/S1367-5931(97)80066-X
  3. Kouzarides, T. Curr. Opin. Genet. Dev. 1999, 9, 40. https://doi.org/10.1016/S0959-437X(99)80006-9
  4. Grunstein, M. Nature 1997, 389, 349. https://doi.org/10.1038/38664
  5. Cheung, W. L.; Briggs, S. D.; Allis, C. D. Curr. Opin. Cell Biol. 2000, 12, 326. https://doi.org/10.1016/S0955-0674(00)00096-X
  6. Chunaram, C.; Chanchal, K.; Florian, G.; Michael, L. N.; Michael, R.; Tobias, C. W.; Jesper, V. O.; Matthias, M. Science 2009, 325, 834. https://doi.org/10.1126/science.1175371
  7. 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. https://doi.org/10.1016/j.bmcl.2006.09.085
  8. Glaser, K. B. Biochem. Pharm. 2007, 74, 659. https://doi.org/10.1016/j.bcp.2007.04.007
  9. Rodriquez, M.; Aquino, M.; Bruno, I.; De Martino, G.; Taddei, M.; Gomez-Paloma, L. Curr. Med. Chem. 2006, 13, 1119. https://doi.org/10.2174/092986706776360905
  10. Dokmanovic, M.; Marks, P. A. J. Cell. Biochem. 2005, 96, 293. https://doi.org/10.1002/jcb.20532
  11. Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Nat. Rev. Drug Discov. 2006, 5, 769. https://doi.org/10.1038/nrd2133
  12. Minucci, S.; Pelicci, P. G. Nat. Rev. Cancer 2006, 6, 38. https://doi.org/10.1038/nrc1779
  13. 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. https://doi.org/10.1111/j.1349-7006.2001.tb02153.x
  14. 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. https://doi.org/10.1074/jbc.M510023200
  15. Glaser, K. B.; Li, J.; Staver, M. J.; Wei, R.-Q.; Albert, D. H.; Davidsen, S. K. Biochem. Biophys. Res. Commun. 2003, 310, 529. https://doi.org/10.1016/j.bbrc.2003.09.043
  16. Altucci, L.; Rossin, A.; Raelsberger, W.; Reitmair, A.; Chomienne, C.; Gronemeyer, H. Nat. Med. 2001, 7, 680. https://doi.org/10.1038/89050
  17. Inoue, S.; Mai, A.; Dyer, M. J. S.; Cohen, G. M. Cancer Res. 2006, 66, 6785. https://doi.org/10.1158/0008-5472.CAN-05-4563
  18. 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. https://doi.org/10.1038/nm1161
  19. Karagiannis, T. C.; El-Osta, A. Leukemia 2007, 21, 61. https://doi.org/10.1038/sj.leu.2404464
  20. 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. https://doi.org/10.1128/MCB.00494-07
  21. Grant, S.; Easley, C.; Kirkpatrick, P. Nat. Rev. Drug Disc. 2007, 6, 21. https://doi.org/10.1038/nrd2227
  22. Suzuki, T.; Ando, T.; Tsuchiya, K.; Fukazawa, N.; Saito, A.; Mariko, Y.; Yamashita, T.; Nakanishi, O. J. Med. Chem. 1999, 42, 3001. https://doi.org/10.1021/jm980565u
  23. 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. https://doi.org/10.1021/jm800251w
  24. Liu, L.; Chen, B.; Qin, S.; Li, S.; He, X.; Qiu, S.; Zhao, W.; Zhao, H. Biochem Biophys Res. Commun. 2010, 392, 190. https://doi.org/10.1016/j.bbrc.2010.01.011
  25. Moradei, O.; Vaisburg, A.; Martell, R. E. Curr. Top. Med. Chem. 2008, 8, 841. https://doi.org/10.2174/156802608784911581
  26. Miller, T. A.; Witter, D. J.; Belvedere, S. J. J. Med. Chem. 2003, 46, 5097. https://doi.org/10.1021/jm0303094
  27. Mitra, A. K.; De, A.; Karchaudhuri, N. Synthetic Commun. 1999, 29, 573. https://doi.org/10.1080/00397919908085805

Cited by

  1. Thermodynamic Characteristics and Spectral-Luminescent Properties of N-m-Tolylbenzamide in Microheterogeneous Surfactant Self-Assemblies vol.43, pp.3, 2014, https://doi.org/10.1007/s10953-014-0151-x
  2. Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents vol.132, pp.None, 2012, https://doi.org/10.1016/j.ejmech.2017.03.024
  3. Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities vol.117, pp.None, 2012, https://doi.org/10.1016/j.bioorg.2021.105407