3-substituted-N-(4-hydroxynaphthalen-1-yl)arylsulfonamides as a novel class of selective Mcl-1 inhibitors: Structure-based design, synthesis, SAR, and biological evaluation

Journal of Medicinal Chemistry

Volumn 57, Issue 10, 2014, Pages 4111-4133

  Abulwerdi, Fardokht A ^a,b   Liao, Chenzhong ^a,c   Mady, Ahmed S ^a,b   Gavin, Jordan ^a   Shen, Chenxi ^a   Cierpicki, Tomasz ^a   Stuckey, Jeanne A ^b   Showalter, H D Hollis ^b   Nikolovska Coleska, Zaneta ^a,b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c HEFEI UNIVERSITY OF TECHNOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[1 HYDROXY 4 (2 PHENYLACETAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (4 METHOXYPHENYLSULFONAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (4 PHENOXYPHENYLSULFONAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (4 PHENYLPIPERAZINE 1 SULFONAMIDO) NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (METHYLSULFONAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (PHENYLSULFONAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[1 HYDROXY 4 (THIOPHENE 2 SULFONAMIDO)NAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (2 BROMOPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (2',4' DIFLUORO [1,1' BIPHENYL] 4 YLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (3 BROMOPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (4 BROMOBENZAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (4 BROMOPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETAMIDE; 2 [[4 (4 BROMOPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (4 CHLOROPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (4' CHLORO [1,1' BIPHENYL] 4 YLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 (BENZO[B]THIOPHENE 2 SULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 ([1,1' BIPHENYL] 2 YLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 ([1,1' BIPHENYL] 3 YLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 ([1,1' BIPHENYL] 4 YLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 [(4 CHLOROPHENYL)METHYLSULFONAMIDO] 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 [2 (4 CHLOROPHENYL)ACETAMIDO] 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 2 [[4 [4 (4 FLUOROPHENOXY)PHENYLSULFONAMIDO] 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETIC ACID; 3 SUBSTITUTED N (4 HYDROXYNAPHTHALEN 1 YL)ARYLSULFONAMIDE; 4 BROMO N [3 (BUTYLTHIO) 4 HYDROXYNAPHTHALEN 1 YL] BENZENESULFONAMIDE; 4 BROMO N [4 HYDROXY 3 (3 HYDROXYPROPYL)NAPHTHALEN 1 YL]BENZENESULFONAMIDE; 4 BROMO N [4 HYDROXY 3 (4 HYDROXYBUTYL)NAPHTHALEN 1 YL]BENZENESULFONAMIDE; ANTINEOPLASTIC AGENT; METHYL 2 [[4 (4 BROMOPHENYLSULFONAMIDO) 1 HYDROXYNAPHTHALEN 2 YL]THIO]ACETATE; SULFONAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

APOPTOSIS; ARTICLE; CELL DEATH; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVATION; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HUMAN; HUMAN CELL; LEUKEMIA CELL LINE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; BCL-2 HOMOLOGOUS ANTAGONIST-KILLER PROTEIN; BCL-2-ASSOCIATED X PROTEIN; CELL LINE, TUMOR; DRUG DESIGN; HUMANS; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 84901280408     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500010b     Document Type: Article

References (86)

1. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: the next generation Cell 2011, 144, 646-674
2. Hanahan, D.; Weinberg, R. A. The hallmarks of cancer Cell 2000, 100, 57-70
3. Fulda, S.; Debatin, K. M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy Oncogene 2006, 25, 4798-4811
4. Youle, R. J.; Strasser, A. The BCL-2 protein family: opposing activities that mediate cell death Nature Rev. Mol. Cell Biol. 2008, 9, 47-59
5. Bajwa, N.; Liao, C.; Nikolovska-Coleska, Z. Inhibitors of the anti-apoptotic Bcl-2 proteins: a patent review Expert Opin. Ther. Pat. 2012, 22, 37-55
6. Lessene, G.; Czabotar, P. E.; Colman, P. M. BCL-2 family antagonists for cancer therapy Nature Rev. Drug Discovery 2008, 7, 989-1000
7. Vogler, M.; Dinsdale, D.; Dyer, M. J.; Cohen, G. M. Bcl-2 inhibitors: small molecules with a big impact on cancer therapy Cell Death Differ. 2009, 16, 360-367
8. Souers, A. J.; Leverson, J. D.; Boghaert, E. R.; Ackler, S. L.; Catron, N. D.; Chen, J.; Dayton, B. D.; Ding, H.; Enschede, S. H.; Fairbrother, W. J.; Huang, D. C.; Hymowitz, S. G.; Jin, S.; Khaw, S. L.; Kovar, P. J.; Lam, L. T.; Lee, J.; Maecker, H. L.; Marsh, K. C.; Mason, K. D.; Mitten, M. J.; Nimmer, P. M.; Oleksijew, A.; Park, C. H.; Park, C. M.; Phillips, D. C.; Roberts, A. W.; Sampath, D.; Seymour, J. F.; Smith, M. L.; Sullivan, G. M.; Tahir, S. K.; Tse, C.; Wendt, M. D.; Xiao, Y.; Xue, J. C.; Zhang, H.; Humerickhouse, R. A.; Rosenberg, S. H.; Elmore, S. W. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets Nature Med. 2013, 19, 202-208
9. Lessene, G.; Czabotar, P. E.; Sleebs, B. E.; Zobel, K.; Lowes, K. N.; Adams, J. M.; Baell, J. B.; Colman, P. M.; Deshayes, K.; Fairbrother, W. J.; Flygare, J. A.; Gibbons, P.; Kersten, W. J.; Kulasegaram, S.; Moss, R. M.; Parisot, J. P.; Smith, B. J.; Street, I. P.; Yang, H.; Huang, D. C.; Watson, K. G. Structure-guided design of a selective BCL-X(L) inhibitor Nature Chem. Biol. 2013, 9, 390-397
10. 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
11. 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
12. Tse, C.; Shoemaker, A. R.; Adickes, J.; Anderson, M. G.; Chen, J.; Jin, S.; Johnson, E. F.; Marsh, K. C.; Mitten, M. J.; Nimmer, P.; Roberts, L.; Tahir, S. K.; Xiao, Y.; Yang, X.; Zhang, H.; Fesik, S.; Rosenberg, S. H.; Elmore, S. W. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor Cancer Res. 2008, 68, 3421-3428
13. Roberts, A. W.; Seymour, J. F.; Brown, J. R.; Wierda, W. G.; Kipps, T. J.; Khaw, S. L.; Carney, D. A.; He, S. Z.; Huang, D. C.; Xiong, H.; Cui, Y.; Busman, T. A.; McKeegan, E. M.; Krivoshik, A. P.; Enschede, S. H.; Humerickhouse, R. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease J. Clin. Oncol. 2012, 30, 488-496
14. van Delft, M. F.; Wei, A. H.; Mason, K. D.; Vandenberg, C. J.; Chen, L.; Czabotar, P. E.; Willis, S. N.; Scott, C. L.; Day, C. L.; Cory, S.; Adams, J. M.; Roberts, A. W.; Huang, D. C. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized Cancer Cell 2006, 10, 389-399
15. Konopleva, M.; Contractor, R.; Tsao, T.; Samudio, I.; Ruvolo, P. P.; Kitada, S.; Deng, X.; Zhai, D.; Shi, Y. X.; Sneed, T.; Verhaegen, M.; Soengas, M.; Ruvolo, V. R.; McQueen, T.; Schober, W. D.; Watt, J. C.; Jiffar, T.; Ling, X.; Marini, F. C.; Harris, D.; Dietrich, M.; Estrov, Z.; McCubrey, J.; May, W. S.; Reed, J. C.; Andreeff, M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia Cancer Cell 2006, 10, 375-388
16. Chauhan, D.; Velankar, M.; Brahmandam, M.; Hideshima, T.; Podar, K.; Richardson, P.; Schlossman, R.; Ghobrial, I.; Raje, N.; Munshi, N.; Anderson, K. C. A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma Oncogene 2007, 26, 2374-2380
17. Chen, S.; Dai, Y.; Harada, H.; Dent, P.; Grant, S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation Cancer Res. 2007, 67, 782-791
18. Lin, X.; Morgan-Lappe, S.; Huang, X.; Li, L.; Zakula, D. M.; Vernetti, L. A.; Fesik, S. W.; Shen, Y. 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737 Oncogene 2007, 26, 3972-3979
19. Moulding, D. A.; Giles, R. V.; Spiller, D. G.; White, M. R.; Tidd, D. M.; Edwards, S. W. Apoptosis is rapidly triggered by antisense depletion of MCL-1 in differentiating U937 cells Blood 2000, 96, 1756-1763
20. Marsden, V. S.; Strasser, A. Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more Annu. Rev. Immunol. 2003, 21, 71-105
21. MacCallum, D. E.; Melville, J.; Frame, S.; Watt, K.; Anderson, S.; Gianella-Borradori, A.; Lane, D. P.; Green, S. R. Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1 Cancer Res. 2005, 65, 5399-5407
22. Zhang, B.; Gojo, I.; Fenton, R. G. Myeloid cell factor-1 is a critical survival factor for multiple myeloma Blood 2002, 99, 1885-1893
23. Michels, J.; O'Neill, J. W.; Dallman, C. L.; Mouzakiti, A.; Habens, F.; Brimmell, M.; Zhang, K. Y.; Craig, R. W.; Marcusson, E. G.; Johnson, P. W.; Packham, G. Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage Oncogene 2004, 23, 4818-4827
24. Song, L.; Coppola, D.; Livingston, S.; Cress, D.; Haura, E. B. Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells Cancer Biol. Ther 2005, 4, 267-276
25. Qin, J. Z.; Xin, H.; Sitailo, L. A.; Denning, M. F.; Nickoloff, B. J. Enhanced killing of melanoma cells by simultaneously targeting Mcl-1 and NOXA Cancer Res. 2006, 66, 9636-9645
26. Miyamoto, Y.; Hosotani, R.; Wada, M.; Lee, J. U.; Koshiba, T.; Fujimoto, K.; Tsuji, S.; Nakajima, S.; Doi, R.; Kato, M.; Shimada, Y.; Imamura, M. Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers Oncology 1999, 56, 73-82
27. Ren, L. N.; Li, Q. F.; Xiao, F. J.; Yan, J.; Yang, Y. F.; Wang, L. S.; Guo, X. Z.; Wang, H. Endocrine glands-derived vascular endothelial growth factor protects pancreatic cancer cells from apoptosis via upregulation of the myeloid cell leukemia-1 protein Biochem. Biophys. Res. Commun. 2009, 386, 35-39
28. Cavarretta, I. T.; Neuwirt, H.; Untergasser, G.; Moser, P. L.; Zaki, M. H.; Steiner, H.; Rumpold, H.; Fuchs, D.; Hobisch, A.; Nemeth, J. A.; Culig, Z. The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1 Oncogene 2007, 26, 2822-2832
29. Chung, T. K.; Cheung, T. H.; Lo, W. K.; Yim, S. F.; Yu, M. Y.; Krajewski, S.; Reed, J. C.; Wong, Y. F. Expression of apoptotic regulators and their significance in cervical cancer Cancer Lett. 2002, 180, 63-68
30. Sieghart, W.; Losert, D.; Strommer, S.; Cejka, D.; Schmid, K.; Rasoul-Rockenschaub, S.; Bodingbauer, M.; Crevenna, R.; Monia, B. P.; Peck-Radosavljevic, M.; Wacheck, V. Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy J. Hepatol 2006, 44, 151-157
31. Cho-Vega, J. H.; Rassidakis, G. Z.; Admirand, J. H.; Oyarzo, M.; Ramalingam, P.; Paraguya, A.; McDonnell, T. J.; Amin, H. M.; Medeiros, L. J. MCL-1 expression in B-cell non-Hodgkin's lymphomas Hum. Pathol. 2004, 35, 1095-1100
32. Khoury, J. D.; Medeiros, L. J.; Rassidakis, G. Z.; McDonnell, T. J.; Abruzzo, L. V.; Lai, R. Expression of Mcl-1 in mantle cell lymphoma is associated with high-grade morphology, a high proliferative state, and p53 overexpression J. Pathol 2003, 199, 90-97
33. Backus, H. H.; van Riel, J. M.; van Groeningen, C. J.; Vos, W.; Dukers, D. F.; Bloemena, E.; Wouters, D.; Pinedo, H. M.; Peters, G. J. Rb, mcl-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer Ann. Oncol. 2001, 12, 779-785
34. Wuilleme-Toumi, S.; Robillard, N.; Gomez, P.; Moreau, P.; Le Gouill, S.; Avet-Loiseau, H.; Harousseau, J. L.; Amiot, M.; Bataille, R. Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival Leukemia 2005, 19, 1248-1252
35. Kaufmann, S. H.; Karp, J. E.; Svingen, P. A.; Krajewski, S.; Burke, P. J.; Gore, S. D.; Reed, J. C. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse Blood 1998, 91, 991-1000
36. Kitada, S.; Andersen, J.; Akar, S.; Zapata, J. M.; Takayama, S.; Krajewski, S.; Wang, H. G.; Zhang, X.; Bullrich, F.; Croce, C. M.; Rai, K.; Hines, J.; Reed, J. C. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses Blood 1998, 91, 3379-3389
37. Gomez-Bougie, P.; Bataille, R.; Amiot, M. The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cells Eur. J. Immunol. 2004, 34, 3156-3164
38. Gomez-Bougie, P.; Wuilleme-Toumi, S.; Menoret, E.; Trichet, V.; Robillard, N.; Philippe, M.; Bataille, R.; Amiot, M. Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma Cancer Res. 2007, 67, 5418-5424
39. Hussain, S. R.; Cheney, C. M.; Johnson, A. J.; Lin, T. S.; Grever, M. R.; Caligiuri, M. A.; Lucas, D. M.; Byrd, J. C. Mcl-1 is a relevant therapeutic target in acute and chronic lymphoid malignancies: down-regulation enhances rituximab-mediated apoptosis and complement-dependent cytotoxicity Clin. Cancer Res. 2007, 13, 2144-2150
40. Thallinger, C.; Wolschek, M. F.; Wacheck, V.; Maierhofer, H.; Gunsberg, P.; Polterauer, P.; Pehamberger, H.; Monia, B. P.; Selzer, E.; Wolff, K.; Jansen, B. Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model J. Invest. Dermatol. 2003, 120, 1081-1086
41. Wei, S. H.; Dong, K.; Lin, F.; Wang, X.; Li, B.; Shen, J. J.; Zhang, Q.; Wang, R.; Zhang, H. Z. Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell Cancer Chemother. Pharmacol. 2008, 62, 1055-1064
42. Guoan, X.; Hanning, W.; Kaiyun, C.; Hao, L. Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo Surgery 2010, 147, 553-561
43. Abulwerdi, F.; Liao, C.; Liu, M.; Azmi, A. S.; Aboukameel, A.; Mady, A. S.; Gulappa, T.; Cierpicki, T.; Owens, S.; Zhang, T.; Sun, D.; Stuckey, J. A.; Mohammad, R. M.; Nikolovska-Coleska, Z. A Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In Vitro and In Vivo Mol. Cancer Ther 2014, 13, 565
44. Tanaka, Y.; Aikawa, K.; Nishida, G.; Homma, M.; Sogabe, S.; Igaki, S.; Hayano, Y.; Sameshima, T.; Miyahisa, I.; Kawamoto, T.; Tawada, M.; Imai, Y.; Inazuka, M.; Cho, N.; Imaeda, Y.; Ishikawa, T. Discovery of potent Mcl-1/Bcl-xL dual inhibitors by using a hybridization strategy based on structural analysis of target proteins J. Med. Chem. 2013, 56, 9635-9645
45. Friberg, A.; Vigil, D.; Zhao, B.; Daniels, R. N.; Burke, J. P.; Garcia-Barrantes, P. M.; Camper, D.; Chauder, B. A.; Lee, T.; Olejniczak, E. T.; Fesik, S. W. Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design J. Med. Chem. 2013, 56, 15-30
46. Song, T.; Li, X.; Chang, X.; Liang, X.; Zhao, Y.; Wu, G.; Xie, S.; Su, P.; Wu, Z.; Feng, Y.; Zhang, Z. 3-Thiomorpholin-8-oxo-8 H -acenaphtho[1,2- b ]pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1 Bioorg. Med. Chem. 2013, 21, 11-20
47. Cohen, N. A.; Stewart, M. L.; Gavathiotis, E.; Tepper, J. L.; Bruekner, S. R.; Koss, B.; Opferman, J. T.; Walensky, L. D. A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-Dependent Leukemia Cell Survival Chem. Biol. 2012, 19, 1175-1186
48. Doi, K.; Li, R.; Sung, S. S.; Wu, H.; Liu, Y.; Manieri, W.; Krishnegowda, G.; Awwad, A.; Dewey, A.; Liu, X.; Amin, S.; Cheng, C.; Qin, Y.; Schonbrunn, E.; Daughdrill, G.; Loughran, T. P., Jr.; Sebti, S.; Wang, H. G. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation J. Biol. Chem. 2012, 287, 10224-10235
49. Rega, M. F.; Wu, B.; Wei, J.; Zhang, Z.; Cellitti, J. F.; Pellecchia, M. SAR by interligand nuclear overhauser effects (ILOEs) based discovery of acylsulfonamide compounds active against Bcl-x(L) and Mcl-1 J. Med. Chem. 2011, 54, 6000-6013
50. Bernardo, P. H.; Sivaraman, T.; Wan, K. F.; Xu, J.; Krishnamoorthy, J.; Song, C. M.; Tian, L.; Chin, J. S.; Lim, D. S.; Mok, H. Y.; Yu, V. C.; Tong, J. C.; Chai, C. L. Structural insights into the design of small molecule inhibitors that selectively antagonize Mcl-1 J. Med. Chem. 2010, 53, 2314-2318
51. Stewart, M. L.; Fire, E.; Keating, A. E.; Walensky, L. D. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer Nature Chem. Biol. 2010, 6, 595-601
52. Muppidi, A.; Doi, K.; Edwardraja, S.; Drake, E. J.; Gulick, A. M.; Wang, H. G.; Lin, Q. Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors J. Am. Chem. Soc. 2012, 134, 14734-14737
53. Ge, Y.; Kazi, A.; Marsilio, F.; Luo, Y.; Jain, S.; Brooks, W.; Daniel, K. G.; Guida, W. C.; Sebti, S. M.; Lawrence, H. R. Discovery and synthesis of hydronaphthoquinones as novel proteasome inhibitors J. Med. Chem. 2012, 55, 1978-1998
54. Abad-Zapatero, C.; Metz, J. T. Ligand efficiency indices as guideposts for drug discovery Drug Discovery Today 2005, 10, 464-469
55. Schrödinger Suite 2011 Induced Fit Docking protocol: Glide Version 5.7; Schrödinger, LLC: New York, NY, 2009
56. Prime Version 3.0; Schrödinger, LLC: New York, NY., 2011.
57. Czabotar, P. E.; Lee, E. F.; van Delft, M. F.; Day, C. L.; Smith, B. J.; Huang, D. C.; Fairlie, W. D.; Hinds, M. G.; Colman, P. M. Structural insights into the degradation of Mcl-1 induced by BH3 domains Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 6217-6222
58. Lee, E. F.; Czabotar, P. E.; van Delft, M. F.; Michalak, E. M.; Boyle, M. J.; Willis, S. N.; Puthalakath, H.; Bouillet, P.; Colman, P. M.; Huang, D. C.; Fairlie, W. D. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation J. Cell Biol. 2008, 180, 341-355
59. Yang, C. Y.; Wang, S. M. Analysis of Flexibility and Hotspots in Bcl-xL and Mcl-1 Proteins for the Design of Selective Small-Molecule Inhibitors ACS Med. Chem. Lett. 2012, 3, 308-312
60. Liu, Q.; Moldoveanu, T.; Sprules, T.; Matta-Camacho, E.; Mansur-Azzam, N.; Gehring, K. Apoptotic regulation by MCL-1 through heterodimerization J. Biol. Chem. 2010, 285, 19615-19624
61. Castanet, A. S.; Colobert, F.; Broutin, P. E. Mild and regioselective iodination of electron-rich aromatics with N -iodosuccinimide and catalytic trifluoroacetic acid Tetrahedron Lett. 2002, 43, 5047-5048
62. Ciattini, P. G.; Morera, E.; Ortar, G. A New, Palladium-Catalyzed Synthesis of Aromatic Mercapturic Acid Derivatives Tetrahedron Lett. 1995, 36, 4133-4136
63. Dai, W.; Petersen, J. L.; Wang, K. K. Synthesis of the parent and substituted tetracyclic ABCD ring cores of camptothecins via 1-(3-aryl-2-propynyl)-1,6-dihydro-6-oxo-2-pyridinecarbonitriles Org. Lett. 2006, 8, 4665-4667
64. Eichman, C. C.; Stambuli, J. P. Zinc-mediated palladium-catalyzed formation of carbon-sulfur bonds J. Org. Chem. 2009, 74, 4005-4008
65. Itoh, T.; Mase, T. A general palladium-catalyzed coupling of aryl bromides/triflates and thiols Org. Lett. 2004, 6, 4587-4590
66. Mispelaere-Canivet, C.; Spindler, J. F.; Perrio, S.; Beslin, P. Pd-2(dba)(3)/Xantphos-catalyzed cross-coupling of thiols and aryl bromides/triflates Tetrahedron 2005, 61, 5253-5259
67. Riesgo, E. C.; Jin, X.; Thummel, R. P. Introduction of Benzo[ h ]quinoline and 1,10-Phenanthroline Subunits by Friedlander Methodology J. Org. Chem. 1996, 61, 3017-3022
68. Ortar, G.; Cascio, M. G.; De Petrocellis, L.; Morera, E.; Rossi, F.; Schiano-Moriello, A.; Nalli, M.; de Novellis, V.; Woodward, D. F.; Maione, S.; Di Marzo, V. New N -arachidonoylserotonin analogues with potential "dual" mechanism of action against pain J. Med. Chem. 2007, 50, 6554-6569
69. Beaudoin, S.; Kinsey, K. E.; Burns, J. F. Preparation of unsymmetrical sulfonylureas from N, N′-sulfuryldiimidazoles J. Org. Chem. 2003, 68, 115-119
70. Greig, I. R.; Idris, A. I.; Ralston, S. H.; van't Hof, R. J. Development and characterization of biphenylsulfonamides as novel inhibitors of bone resorption J. Med. Chem. 2006, 49, 7487-7492
71. Li, X.; Chu, S.; Feher, V. A.; Khalili, M.; Nie, Z.; Margosiak, S.; Nikulin, V.; Levin, J.; Sprankle, K. G.; Tedder, M. E.; Almassy, R.; Appelt, K.; Yager, K. M. Structure-based design, synthesis, and antimicrobial activity of indazole-derived SAH/MTA nucleosidase inhibitors J. Med. Chem. 2003, 46, 5663-5673
72. Wagner, J.; von Matt, P.; Faller, B.; Cooke, N. G.; Albert, R.; Sedrani, R.; Wiegand, H.; Jean, C.; Beerli, C.; Weckbecker, G.; Evenou, J. P.; Zenke, G.; Cottens, S. Structure-activity relationship and pharmacokinetic studies of sotrastaurin (AEB071), a promising novel medicine for prevention of graft rejection and treatment of psoriasis J. Med. Chem. 2011, 54, 6028-6039
73. Ishizuka, N.; Matsumura, K.; Sakai, K.; Fujimoto, M.; Mihara, S.; Yamamori, T. Structure-activity relationships of a novel class of endothelin-A receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2 H -chromene-3-carbox ylic acid (S-1255). 1. Study on structure-activity relationships and basic structure crucial for ET(A) antagonism J. Med. Chem. 2002, 45, 2041-2055
74. England, D. B.; Kerr, M. A. Synthesis and cross-coupling reactions of substituted 5-triflyloxyindoles J. Org. Chem. 2005, 70, 6519-6522
75. Hajduk, P. J.; Bures, M.; Praestgaard, J.; Fesik, S. W. Privileged molecules for protein binding identified from NMR-based screening J. Med. Chem. 2000, 43, 3443-3447
76. Medek, A.; Hajduk, P. J.; Mack, J.; Fesik, S. W. The use of differential chemical shifts for determining the binding site location and orientation of protein-bound ligands J. Am. Chem. Soc. 2000, 122, 1241-1242
77. Williamson, M. P. Using chemical shift perturbation to characterise ligand binding Prog. Nucl. Magn. Reson. Spectrosc. 2013, 73, 1-16
78. 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
79. Smits, C.; Czabotar, P. E.; Hinds, M. G.; Day, C. L. Structural plasticity underpins promiscuous binding of the prosurvival protein A1 Structure 2008, 16, 818-829
80. Wei, M. C.; Zong, W. X.; Cheng, E. H.; Lindsten, T.; Panoutsakopoulou, V.; Ross, A. J.; Roth, K. A.; MacGregor, G. R.; Thompson, C. B.; Korsmeyer, S. J. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death Science 2001, 292, 727-730
81. Lindsten, T.; Thompson, C. B. Cell death in the absence of Bax and Bak Cell Death Differ. 2006, 13, 1272-1276
82. Whitecross, K. F.; Alsop, A. E.; Cluse, L. A.; Wiegmans, A.; Banks, K. M.; Coomans, C.; Peart, M. J.; Newbold, A.; Lindemann, R. K.; Johnstone, R. W. Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors Blood 2009, 113, 1982-1991
83. Glaser, S. P.; Lee, E. F.; Trounson, E.; Bouillet, P.; Wei, A.; Fairlie, W. D.; Izon, D. J.; Zuber, J.; Rappaport, A. R.; Herold, M. J.; Alexander, W. S.; Lowe, S. W.; Robb, L.; Strasser, A. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia Genes Dev. 2012, 26, 120-125
84. Murugesan, N.; Hunt, J. T.; Stein, P. D. Preparation of phenylsulfonamidooxazole and -isoxazole endothelin antagonists. US5514696A, 1996.
85. Lewis, I. A.; Schommer, S. C.; Markley, J. L. rNMR: open source software for identifying and quantifying metabolites in NMR spectra Magn. Reson. Chem. 2009, 47 (Suppl 1) S123-126
86. Goddard, T. D.; Kneller, D. G. SPARKY 3; University of California: San Francisco, 2006.