Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists

Journal of Medicinal Chemistry

Volumn 54, Issue 21, 2011, Pages 7693-7704

  Guo, Chuangxing ^a   Linton, Angelica ^a   Kephart, Susan ^a   Ornelas, Martha ^a   Pairish, Mason ^a   Gonzalez, Javier ^a   Greasley, Samantha ^a   Nagata, Asako ^a   Burke, Benjamin J ^a   Edwards, Martin ^a   Hosea, Natilie ^a   Kang, Ping ^a   Hu, Wenyue ^a   Engebretsen, Jon ^a   Briere, David ^a   Shi, Manli ^a   Gukasyan, Hovik ^a   Richardson, Paul ^a   Dack, Kevin ^b   Underwood, Toby ^b   Johnson, Patrick ^b   Morell, Andrew ^b   Felstead, Robert ^b   Kuruma, Hidetoshi ^c   Matsimoto, Hiroaki ^c   Zoubeidi, Amina ^c   Gleave, Martin ^c   Los, Gerrit ^a   Fanjul, Andrea N ^a   more..

^a PFIZER INC   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; ANDROGEN RECEPTOR ANTAGONIST; BICALUTAMIDE; CYCLOBUTANE DERIVATIVE; N [3 (3 CHLORO 4 CYANOPHENOXY) 2,2,4,4 TETRAMETHYLCYCLOBUTYL] 1 (2 HYDROXYETHYL) 1H PYRAZOLE 4 CARBOXAMIDE; N [3 (3,4 DICYANOPHENOXY) 2,2,4,4 TETRAMETHYLCYCLOBUTYL]ACETAMIDE; N [3 (5 CYANO 6 METHYLPYRIDIN 2 YLOXY) 2,2,4,4 TETRAMETHYLCYCLOBUTYL]IMIDAZO[1,2 A]PYRIMIDINE 3 CARBOXAMIDE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; PROSTATE SPECIFIC ANTIGEN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CANCER MODEL; CASTRATION RESISTANT PROSTATE CANCER; DRUG CONFORMATION; DRUG EFFICACY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT;

ADMINISTRATION, ORAL; ANDROGEN ANTAGONISTS; ANDROGENS; ANIMALS; ANTINEOPLASTIC AGENTS; BICYCLO COMPOUNDS, HETEROCYCLIC; CELL LINE; CYCLOBUTANES; DRUG RESISTANCE, NEOPLASM; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; LIGANDS; MALE; MICE; MICE, NUDE; MODELS, MOLECULAR; PROSTATIC NEOPLASMS; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 80455162581     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201059s     Document Type: Article

References (24)

1. Chen, Y.; Sawyers, C. L.; Scher, H. I. Targeting the androgen receptor pathway in prostate cancer Curr. Opin. Pharmacol. 2008, 8, 440-448
2. Schellhammer, P. An update on bicalutamide in the treatment of prostate cancer Expert Opin. Invest. Drugs 1999, 8, 849-860
3. Kelly, W. K.; Slovin, S.; Scher, H. I. Steroid hormone withdrawal syndromes. Pathophysiology and clinical significance Urol. Clin. North Am. 1997, 24, 421-431
4. Chen, C. D.; Welsbie, D. S.; Tran, C.; Baek, S. H.; Chen, R.; Vessella, R.; Rosenfeld, M. G.; Sawyers, C. L. Molecular determinants of resistance to antiandrogen therapy Nat. Med. 2004, 10, 33-39
5. Jung, M. E.; Ouk, S.; Yoo, D.; Sawyers, C. L.; Chen, C.; Tran, C.; Wongvipat, J. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC) J. Med. Chem. 2010, 53, 2779-96
6. Tran, C.; Ouk, S.; Clegg, N. J.; Chen, Y.; Watson, P. A.; Arora, V.; Wongvipat, J.; Smith-Jones, P. M.; Yoo, D.; Kwon, A.; Wasielewska, T.; Welsbie, D.; Chen, C. D.; Higano, C. S.; Beer, T. M.; Hung, D. T.; Scher, H. I.; Jung, M. E.; Sawyers, C. L. Development of a second-generation antiandrogen for treatment of advanced prostate cancer Science 2009, 324, 787-790
7. Attar, R. M.; Jure-Kunkel, M.; Balog, A.; Cvijic, M. E.; Dell-John, J.; Rizzo, C. A.; Schweizer, L.; Spires, T. E.; Platero, J. S.; Obermeier, M.; Shan, W.; Salvati, M. E.; Foster, W. R.; Dinchuk, J.; Chen, S. J.; Vite, G.; Kramer, R.; Gottardis, M. M. Discovery of BMS-641988, a novel and potent inhibitor of androgen receptor signaling for the treatment of prostate cancer Cancer Res. 2009, 69, 6522-6530
8. Salvati, M. E.; Balog, A.; Shan, W.; Rampulla, R.; Giese, S.; Mitt, T.; Furch, J. A.; Vite, G. D.; Attar, R. M.; Jure-Kunkel, M.; Geng, J.; Rizzo, C. A.; Gottardis, M. M.; Krystek, S. R.; Gougoutas, J.; Galella, M. A.; Obermeier, M.; Fura, A.; Chandrasena, G. Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists Bioorg. Med. Chem. Lett. 2008, 18, 1910-1915
9. Salvati, M. E.; Balog, A.; Shan, W.; Wei, D. D.; Pickering, D.; Attar, R. M.; Geng, J.; Rizzo, C. A.; Gottardis, M. M.; Weinmann, R.; Krystek, S. R.; Sack, J.; An, Y.; Kish, K. Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists Bioorg. Med. Chem. Lett. 2005, 15, 271-276
10. Salvati, M. E.; Balog, A.; Wei, D. D.; Pickering, D.; Attar, R. M.; Geng, J.; Rizzo, C. A.; Hunt, J. T.; Gottardis, M. M.; Weinmann, R.; Martinez, R. Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus Bioorg. Med. Chem. Lett. 2005, 15, 389-393
11. Scher, H. I.; Beer, T. M.; Higano, C. S.; Anand, A.; Taplin, M.-E.; Efstathiou, E.; Rathkopf, D.; Shelkey, J.; Yu, E. Y.; Alumkal, J.; Hung, D.; Hirmand, M.; Seely, L.; Morris, M. J.; Danila, D. C.; Humm, J.; Larson, S.; Fleisher, M.; Sawyers, C. L. Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium Lancet 2010, 375, 1437-1446
12. Ryckmans, T.; Edwards, M. P.; Horne, V. A.; Correia, A. M.; Owen, D. R.; Thompson, L. R.; Tran, I.; Tutt, M. F.; Young, T. Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis Bioorg. Med. Chem. Lett. 2009, 19, 4406-4409
13. Stephan, C.; Cammann, H.; Meyer, H. A.; Lein, M.; Jung, K. PSA and new biomarkers within multivariate models to improve early detection of prostate cancer Cancer Lett. 2007, 249, 18-29
14. Pereira De Jesus-Tran, K.; Cote, P.; Cantin, L.; Blanchet, J.; Labrie, F; Breton, R. Comparison of crystal structures of human androgen receptor-ligand domain complexed with various agonists reveals molecular determinants responsible for binding affinity Protein Sci. 2006, 15, 987-999
15. De Bellis, A.; Quigley, C. S.; Cariello, N. F.; El-Awady, M. K.; Sar, M.; Lane, M. V.; Wilson, E. M.; French, F. S. Single base mutations in the androgen receptor gene causing complete androgen insensitivity: Rapid detections by a modified denaturing gradient gel electrophoresis technique Mol. Endocrinol. 1992, 6, 1909-1920
16. Pinsky, L.; Trifiro, M.; Kaufman, M.; Beitel, L. K.; Mhatre, A.; Kazemi-Esfarjani, P.; Sabbaghian, N.; Lumbroso, R.; Alvarado, C.; Vasiliou, M. Androgen resistance due to mutation of the androgen receptor Clin. Invest. Med. 1992, 15, 456-472
17. Hur, E.; Pfaff, S. J.; Payne, E. S.; Gron, H.; Buehrer, B. M.; Fletterick, R. J. Recognition and accommodation at the androgen receptor coactivator binding interface PLoS Biol. 2004, 2, E274
18. Shiau, A. K.; Barstad, D.; Loria, P. M.; Cheng, L.; Kushner, P. J.; Agard, D. A.; Greene, G. L. The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen Cell 1998, 95, 927-937
19. Webb, P.; Nguyen, N.; Chiellini, G.; Yoshihara, H. A. I.; Cunha Lima, S. T.; Apriletti, J. W.; Ribeiro, R. C. J.; Marimuthu, A.; West, B. L.; Goede, P.; Mellstrom, K.; Nilsson, S.; Kushner, P. J.; Fletterick, R. J.; Scanlan, T. S.; Baxter, J. D. Design of thyroid hormone receptor antagonists from first principles J. Steroid Biochem. Mol. Biol. 2003, 83, 59-73
20. Pike, A. C. W.; Brzozowski, A. M.; Hubbard, R. E.; Bonn, T.; Thorsell, A. G.; Engstro, O.; Ljunggren, J.; Gustafsson, J.; Carlquist, M. Structure of the ligand binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist EMBO J. 1999, 18, 4608-4618
21. Schoch, G. A.; D'Arcy, B.; Stihle, M.; Burger, D.; Bar, D.; Benz, J.; Thoma, R.; Ruf, A. Molecular Switch in the Glucocorticoid Receptor: Active and Passive Antagonist Conformations J. Mol. Biol. 2010, 568-577
22. Gehlhaar, D. K.; Verkhivker, G. M.; Rejto, P. A.; Sherman, C. J.; Fogel, D. B.; Fogel, L. J.; Freer, S. T. Molecular Recognition of the Inhibitor AG-1343 by HIV-1 Protease: Conformationally Flexible Docking by Evolutionary Programming Chemistry and Biology 1995, 2 (5) 317-324
23. Gehlhaar, D. K.; Bouzida, D.; Rejto, P. A. Reduced Dimensionality in Ligand-Protein Structure Prediction: Covalent Inhibitors of Serine Proteases and Design of Site-Directed Combinatorial Libraries; ACS Symposium Series 719: Rational Drug Design. Parrill, A. L.; M. R. Reddy, Eds. ACS Press, 1999, 292 - 311.
24. Glide, version 5.5, Schrodinger, Inc., New York, NY, 2009.