Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 12, 2011, Pages 3627-3631

  Zapf, Christoph W ^a   Bloom, Jonathan D ^a   McBean, Jamie L ^a   Dushin, Russell G ^a   Golas, Jennifer M ^a   Liu, Hao ^a   Lucas, Judy ^a   Boschelli, Frank ^a   Vogan, Erik ^a   Levin, Jeremy I ^a  

^a PFIZER INC   (United States)

Author keywords

Buchwald Hartwig cyclization; Chaperone inhibitors; Hsp90 inhibitors; Macrocycles; N terminal ATP binding site; Ortho aminobenzamides

Indexed keywords

2 AMINOBENZAMIDE DERIVATIVE; BIOLOGICAL MARKER; HEAT SHOCK PROTEIN 90 INHIBITOR; MACROCYCLIC COMPOUND; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CELL PROLIFERATION; CELL STRAIN; CELL STRAIN HCT116; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG EFFICACY; IN VIVO STUDY; MOUSE; NONHUMAN; TUMOR XENOGRAFT;

AMINES; ANIMALS; BENZAMIDES; BENZOQUINONES; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG DISCOVERY; HSP90 HEAT-SHOCK PROTEINS; HUMANS; INHIBITORY CONCENTRATION 50; LACTAMS, MACROCYCLIC; MACROCYCLIC COMPOUNDS; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEOPLASMS; TUMOR MARKERS, BIOLOGICAL; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 79957861042     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.04.102     Document Type: Article

References (30)

1. Borst, P.; Jonkers, J.; Rottenberg, S. Cell Cycle 2007, 6, 2782.
2. Nobili, S.; Landini, I.; Giglioni, B.; Mini, E. Curr. Drug Targets 2006, 7, 861.
3. Blagg, B. S.; Kerr, T. D. Med. Res. Rev. 2006, 26, 310.
4. Neckers, L. J. Biosci. 2007, 32, 517.
5. Isaacs, J. S.; Xu, W.; Neckers, L. Cancer Cell 2003, 3, 213.
6. Solit, D. B.; Chiosis, G. Drug Discovery Today 2008, 13, 38.
7. Johnson, V. A.; Singh, E. K.; Nazarova, L. A.; Alexander, L. D.; McAlpine, S. R. Curr. Top. Med. Chem. 2010, 10, 1380.
8. Li, Y.; Zhang, T.; Schwartz, S. J.; Sun, D. Drug Resist. Updates 2009, 12, 17.
9. Janin, Y. L. Drug Discovery Today 2010, 15, 342.
10. Winssinger, N.; Fontaine, J. G.; Barluenga, S. Curr. Top. Med. Chem. 2009, 9, 1419.
11. Whitesell, L.; Lindquist, S. L. Nat. Rev. Cancer 2005, 5, 761.
12. Maloney, A.; Workman, P. Expert Opin. Biol. Ther. 2002, 2, 3.
13. Drysdale, M. J.; Brough, P. A. Curr. Top. Med. Chem. 2008, 8, 859.
14. Messaoudi, S.; Peyrat, J. F.; Brion, J. D.; Alami, M. Anticancer Agents Med. Chem. 2008, 8, 761.
15. Taldone, T.; Sun, W.; Chiosis, G. Bioorg. Med. Chem. 2009, 17, 2225.
16. Hwang, M.; Moretti, L.; Lu, B. Curr. Med. Chem. 2009, 16, 3081.
17. Whitesell, L.; Mimnaugh, E. G.; De Costa, B.; Myers, C. E.; Neckers, L. M. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8324.
18. Supko, J. G.; Hickman, R. L.; Grever, M. R.; Malspeis, L. Cancer Chemother. Pharmacol. 1995, 36, 305.
19. Tian, Z. Q.; Liu, Y.; Zhang, D.; Wang, Z.; Dong, S. D.; Carreras, C. W.; Zhou, Y.; Rastelli, G.; Santi, D. V.; Myles, D. C. Bioorg. Med. Chem. 2004, 12, 5317.
20. Brough, P. A.; Aherne, W.; Barril, X.; Borgognoni, J.; Boxall, K.; Cansfield, J. E.; Cheung, K. M.; Collins, I.; Davies, N. G.; Drysdale, M. J.; Dymock, B.; Eccles, S. A.; Finch, H.; Fink, A.; Hayes, A.; Howes, R.; Hubbard, R. E.; James, K.; Jordan, A. M.; Lockie, A.; Martins, V.; Massey, A.; Matthews, T. P.; McDonald, E.; Northfield, C. J.; Pearl, L. H.; Prodromou, C.; Ray, S.; Raynaud, F. I.; Roughley, S. D.; Sharp, S. Y.; Surgenor, A.; Walmsley, D. L.; Webb, P.; Wood, M.; Workman, P.; Wright, L. J. Med. Chem. 2008, 51, 196.
21. Biamonte, M. A.; Van de Water, R.; Arndt, J. W.; Scannevin, R. H.; Perret, D.; Lee, W. C. J. Med. Chem. 2010, 53, 3.
22. Barta, T. E.; Veal, J. M.; Rice, J. W.; Partridge, J. M.; Fadden, R. P.; Ma, W.; Jenks, M.; Geng, L.; Hanson, G. J.; Huang, K. H.; Barabasz, A. F.; Foley, B. E.; Otto, J.; Hall, S. E. Bioorg. Med. Chem. Lett. 2008, 18, 3517.
23. Huang, K. H.; Veal, J. M.; Fadden, R. P.; Rice, J. W.; Eaves, J.; Strachan, J. P.; Barabasz, A. F.; Foley, B. E.; Barta, T. E.; Ma, W.; Silinski, M. A.; Hu, M.; Partridge, J. M.; Scott, A.; DuBois, L. G.; Freed, T.; Steed, P. M.; Ommen, A. J.; Smith, E. D.; Hughes, P. F.; Woodward, A. R.; Hanson, G. J.; McCall, W. S.; Markworth, C. J.; Hinkley, L.; Jenks, M.; Geng, L.; Lewis, M.; Otto, J.; Pronk, B.; Verleysen, K.; Hall, S. E. J. Med. Chem. 2009, 52, 4288.
24. Gopalsamy, A.; Shi, M.; Golas, J.; Vogan, E.; Jacob, J.; Johnson, M.; Lee, F.; Nilakantan, R.; Petersen, R.; Svenson, K.; Chopra, R.; Tam, M. S.; Wen, Y.; Ellingboe, J.; Arndt, K.; Boschelli, F. J. Med. Chem. 2008, 51, 373.
25. Driggers, E. M.; Hale, S. P.; Lee, J.; Terrett, N. K. Nat. Rev. Drug Discov. 2008, 7, 608.
26. Marsault, E.; Peterson, M. L. J. Med. Chem. 2011, 54, 1961.
27. Zapf, C. W.; Bloom, J. D.; McBean, J. L.; Dushin, R. G.; Nittoli, T.; Ingalls, C.; Southerland, A.; Sonye, J. P.; Eid, C. N.; Golas, J. M.; Liu, H.; Boschelli, F.; Vogan, E. M.; Hu, Y.; Levin, J. I. Bioorg. Med. Chem. Lett. 2011, 21, 2278.
28. Zapf, C. W.; Bloom, J. D.; McBean, J. L.; Dushin, R. G.; Nittoli, T.; Otteng, M.; Ingalls, C.; Golas, J. M.; Liu, H.; Lucas, J.; Boschelli, F.; Vogan, E. M.; Hu, Y.; Levin, J. I. Bioorg. Med. Chem. Lett. 2011, in press, doi:10.1016/j.bmcl.2011.03.112.
29. Froelich, O.; Desos, P.; Bonin, M.; Quirion, J.-C.; Husson, H.-P.; Zhu, J. J. Org. Chem. 1996, 61, 6700.
30. The structure has been assigned PDB ID code 3R92.