A potent and highly efficacious Bcl-2/Bcl-xL inhibitor

Journal of Medicinal Chemistry

Volumn 56, Issue 7, 2013, Pages 3048-3067

  Aguilar, Angelo ^a   Zhou, Haibin ^a   Chen, Jianfang ^a   Liu, Liu ^a   Bai, Longchuan ^a   McEachern, Donna ^a   Yang, Chao Yie ^a   Meagher, Jennifer ^a   Stuckey, Jeanne ^a   Wang, Shaomeng ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 (4 CHLOROPHENYL) 1 ISOPROPYL 2 METHYL N(METHYLSULFONYL) 4 [3 [4 (4 NITROPHENYL)PIPERAZIN 1 YL]PHENYL] 1H PYRROLE 3 CARBOXAMIDE; 5 (4 CHLOROPHENYL) 4 (3 IODOPHENYL) 1 ISOPROPYL 2 METHYL N (METHYLSULFONYL) 1H PYRROLE 3 CARBOXAMIDE; ANTINEOPLASTIC AGENT; BM 1074; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN INHIBITOR; PYRROLE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CANCER GROWTH; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TOLERABILITY; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; LUNG SMALL CELL CANCER; MOUSE; NONHUMAN; TUMOR REGRESSION;

ANIMALS; BCL-X PROTEIN; BLOTTING, WESTERN; CELL LINE, TUMOR; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MICE, SCID; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 84876231548     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4001105     Document Type: Article

References (25)

1. Cory, S.; Adams, J. M. Killing cancer cells by flipping the Bcl-2/Bax switch Cancer Cell 2005, 8, 5-6
2. Labi, V.; Erlacher, M.; Kiessling, S.; Villunger, A. BH3-only proteins in cell death initiation, malignant disease and anticancer therapy Cell Death Differ. 2006, 13, 1325-1338
3. Labi, V.; Grespi, F.; Baumgartner, F.; Villunger, A. Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: A breakthrough in anticancer therapy? Cell Death Differ. 2008, 15, 977-987
4. Vaux, D. L.; Cory, S.; Adams, J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells Nature 1988, 335, 440-442
5. Oltersdorf, T.; Elmore, S. W.; Shoemaker, A. R.; Armstrong, R. C.; Augeri, D. J.; Belli, B. A.; Bruncko, M.; Deckwerth, T. L.; Dinges, J.; Hajduk, P. J.; Joseph, M. K.; Kitada, S.; Korsmeyer, S. J.; Kunzer, A. R.; Letai, A.; Li, C.; Mitten, M. J.; Nettesheim, D. G.; Ng, S.; Nimmer, P. M.; O'Connor, J. M.; Oleksijew, A.; Petros, A. M.; Reed, J. C.; Shen, W.; Tahir, S. K.; Thompson, C. B.; Tomaselli, K. J.; Wang, B.; Wendt, M. D.; Zhang, H.; Fesik, S. W.; Rosenberg, S. H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours Nature 2005, 435, 677-681
6. Park, C. M.; Bruncko, M.; Adickes, J.; Bauch, J.; Ding, H.; Kunzer, A.; Marsh, K. C.; Nimmer, P.; Shoemaker, A. R.; Song, X.; Tahir, S. K.; Tse, C.; Wang, X.; Wendt, M. D.; Yang, X.; Zhang, H.; Fesik, S. W.; Rosenberg, S. H.; Elmore, S. W. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins J. Med. Chem. 2008, 51, 6902-6915
7. Zhou, H.; Chen, J.; Meagher, J. L.; Yang, C. Y.; Aguilar, A.; Liu, L.; Bai, L.; Cong, X.; Cai, Q.; Fang, X.; Stuckey, J. A.; Wang, S. Design of Bcl-2 and Bcl-xL inhibitors with subnanomolar binding affinities based upon a new scaffold J. Med. Chem. 2012, 55, 4664-4682
8. Zhou, H.; Aguilar, A.; Chen, J.; Bai, L.; Liu, L.; Meagher, J. L.; Yang, C. Y.; McEachern, D.; Cong, X.; Stuckey, J. A.; Wang, S. Structure-based design of potent Bcl-2/Bcl-xL inhibitors with strong in vivo antitumor activity J. Med. Chem. 2012, 55, 6149-6161
9. Chen, J.; Zhou, H.; Aguilar, A.; Liu, L.; Bai, L.; McEachern, D.; Yang, C. Y.; Meagher, J. L.; Stuckey, J. A.; Wang, S. Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression J. Med. Chem. 2012, 55, 8502-8514
10. Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. Room-temperature palladium-catalyzed amination of aryl bromides and chlorides and extended scope of aromatic C-N bond formation with a commercial ligand J. Org. Chem. 1999, 64, 5575-5580
11. Zhang, H.; Cai, Q.; Ma, D. Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles J. Org. Chem. 2005, 70, 5164-5173
12. Tararov, V.; Korostylev, A.; Boerner, A.; Bobal, P.; Frantisek, J.; Stohandl, J.; Denike, K.; Jeker, N. Process for preparing C5 products and their use for atorvastatin synthesis. EP1705175A1, 2006.
13. Roth, B. D.; Blankley, C. J.; Chucholowski, A. W.; Ferguson, E.; Hoefle, M. L.; Ortwine, D. F.; Newton, R. S.; Sekerke, C. S.; Sliskovic, D. R.; Stratton, C. D.; Wilson, M. W. Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1 H -pyrrol-1-yl)ethyl]-2 H -pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus J. Med. Chem. 1991, 34, 357-366
14. Chen, Q. Y.; Wu, S. W. Methyl fluorosulfonyldifluoroacetate-A new trifluoromethylating agent J. Chem. Soc.-Chem. Commun. 1989, 705-706
15. Wendt, M. D.; Rockway, T. W.; Geyer, A.; McClellan, W.; Weitzberg, M.; Zhao, X.; Mantei, R.; Nienaber, V. L.; Stewart, K.; Klinghofer, V.; Giranda, V. L. Identification of novel binding interactions in the development of potent, selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural analysis, and SAR of N -phenyl amide 6-substitution J. Med. Chem. 2004, 47, 303-324
16. Almansa, C.; Alfon, J.; de Arriba, A. F.; Cavalcanti, F. L.; Escamilla, I.; Gomez, L. A.; Miralles, A.; Soliva, R.; Bartroli, J.; Carceller, E.; Merlos, M.; Garcia-Rafanell, J. Synthesis and structure-activity relationship of a new series of COX-2 selective inhibitors: 1,5-Diarylimidazoles J. Med. Chem. 2003, 46, 3463-3475
17. Yang, J.; Teng, Y.; Ara, S.; Rallapalli, S.; Cook, J. M. An improved process for the synthesis of 4 H -Imidazo[1,5- a ][1,4]benzodiazepines Synthesis (Stuttg) 2009, 40, nihpa145687
18. Menozzi, G.; Fossa, P.; Cichero, E.; Spallarossa, A.; Ranise, A.; Mosti, L. Rational design, synthesis and biological evaluation of new 1,5-diarylpyrazole derivatives as CB1 receptor antagonists, structurally related to rimonabant Eur. J. Med. Chem. 2008, 43, 2627-2638
19. Lange, J. H.; van Stuivenberg, H. H.; Coolen, H. K.; Adolfs, T. J.; McCreary, A. C.; Keizer, H. G.; Wals, H. C.; Veerman, W.; Borst, A. J.; de Looff, W.; Verveer, P. C.; Kruse, C. G. Bioisosteric replacements of the pyrazole moiety of rimonabant: Synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists J. Med. Chem. 2005, 48, 1823-1838
20. Olivera, R.; SanMartin, R.; Dominguez, E. A combination of tandem amine-exchange/heterocyclization and biaryl coupling reactions for the straightforward preparation of phenanthro[9,10- d ]pyrazoles J. Org. Chem. 2000, 65, 7010-7019
21. Habeeb, A. G.; Rao, P. N. P.; Knaus, E. E. Design and syntheses of diarylisoxazoles: Novel inhibitors of cyclooxygenase-2 (COX-2) with analgesic-antiinflammatory activity Drug Dev. Res. 2000, 51, 273-286
22. Kajino, M.; Hasuoka, A.; Nishida, H. Preparation of substituted 1-heterocyclylsulfonyl-2-aminomethyl-5-(hetero)aryl-1 H -pyrrole derivatives as acid secretion inhibitors for treating ulcer and related disorders. WO2007026916A1, 2007.
23. Schmidt, A.; Habeck, T.; Kindermann, M. K.; Nieger, M. New pyrazolium-carboxylates as structural analogues of the pseudo-cross-conjugated betainic alkaloid Nigellicine J. Org. Chem. 2003, 68, 5977-5982
24. 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. 4,5-Diarylisoxazole Hsp90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer J. Med. Chem. 2008, 51, 196-218
25. Nikolovska-Coleska, Z.; Wang, R.; Fang, X.; Pan, H.; Tomita, Y.; Li, P.; Roller, P. P.; Krajewski, K.; Saito, N. G.; Stuckey, J. A.; Wang, S. Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization Anal. Biochem. 2004, 332, 261-273