ERβ ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERβ selectivity

Journal of Medicinal Chemistry

Volumn 48, Issue 12, 2005, Pages 3953-3979

  Mewshaw, Richard E ^a   Edsall Jr , Richard J ^a   Yang, Cuijian ^a   Manas, Eric S ^a   Xu, Zhang B ^a   Henderson, Ruth A ^a   Keith Jr , James C ^a   Harris, Heather A ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 CHLORO 6 (4 HYDROXYPHENYL) 2 NAPHTHOL; 2 PHENYLNAPHTHALENE; 3 (3 FLUORO 4 HYDROXYPHENYL) 7 HYDROXY 1 NAPHTHONITRILE; ESTROGEN RECEPTOR BETA; GENISTEIN; NAPHTHALENE DERIVATIVE; NAPHTHOL DERIVATIVE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SOMATOMEDIN BINDING PROTEIN 4; UNCLASSIFIED DRUG; WAY 169122; WAY 202196; 3-(3-FLUORO-4-HYDROXYPHENYL)-7-HYDROXY-1-NAPHTHONITRILE; LIGAND; NONSTEROID ANTIINFLAMMATORY AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BINDING; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LIGAND BINDING; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TRANSGENIC ANIMAL; X RAY ANALYSIS; ANIMAL; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG EFFECT; DRUG POTENTIATION; ENTERITIS; FEMALE; GENETIC TRANSCRIPTION; HISTOLOGY; LEWIS RAT; MALE; MOLECULAR MIMICRY; ORGAN SIZE; SYNTHESIS; TUMOR CELL LINE; UTERUS; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARTHRITIS, EXPERIMENTAL; BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; ESTROGEN RECEPTOR BETA; FEMALE; GENISTEIN; HUMANS; INFLAMMATORY BOWEL DISEASES; LIGANDS; MALE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; NAPHTHALENES; NAPHTHOLS; ORGAN SIZE; RATS; RATS, INBRED LEW; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTION, GENETIC; UTERUS;

EID: 20444387545     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm058173s     Document Type: Article

References (44)

1. Green, S.; Walter, P.; Kumar, V.; Krust, A.; Bornert, J. M.; Argos, P.; Chambon, P. Human oestrogen receptor cDNA: Sequence, expression and homology to v-erb-A. Nature 1986, 320, 134-139.
2. Kuiper, G. G. J. M.; Enmark, E.; Pelto Huikko, M.; Nilsson, S.; Gustafsson, J. A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. U.S.A 1996, 93, 5925-5930.
3. Mosselman, S.; Polman J.; Dijkema, R. ER beta: Identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996, 392, 49-53.
4. Couse, J. F.; Lindzey, J.; Grandien, K.; Gustafsson, J. A.; Korach, K. S. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology 1997, 138, 4613-4621.
5. Fitzpatrick, S. L.; Funkhouser, J. M.; Sindoni, D. M.; Stevis, P. E.; Deecher, D. C.; Bapat, A. R.; Merchenthaler, I.; Frail, D. E. Expression of estrogen receptor-beta protein in rodent ovary. Endocrinology 1999, 140, 2581-2591.
6. Kuiper, G. G. J. M.; Carlsson, B.; Grandian, K.; Enmark, E.; Haggblad, J.; Nilsson, S.; Gustafsson, J. A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptor alpha and beta. Endocrinology 1997, 138, 863-870.
7. Yang, C. J.; Edsall, R.; Harris, H. A.; Zhang, X. C.; Manas, E. S.; Mewshaw, R. E. ERβ ligands. Part 2: Synthesis and structure-activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivatives. Bioorg. Med. Chem. 2004, 12, 2553-2570.
8. Edsall, R. J.; Harris, H. A.; Manas, E. S.; Mewshaw, R. E. ER beta ligands. Part 1: The discovery of ERβ selective ligands which embrace the 4-hydroxy-biphenyl template. Bioorg. Med. Chem. 2003, 11, 3457-3474.
9. Meyers, M. J.; Sun, J.; Carlson, K. E.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Estrogen receptor subtype-selective ligands: Asymmetric synthesis and biological evaluation of cis- and trans-5, 11-dialkyl-5,6,11,12- tetrahydrochrysenes. J. Med. Chem. 1999, 42, 2456-2468.
10. Meyers, M. J.; Sun, J.; Carlson, K. E.; Marriner, G. A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Estrogen receptor-beta potency-selective ligands: Structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J. Med. Chem. 2001, 44, 4230-4251.
11. Schopfer, U.; Schoeffter, P.; Bischoff, S. F.; Nozulak, J.; Feuerbach, D.; Floersheim, P. Toward selective ER beta Agonists for central nervous system disorders: Synthesis and characterization of aryl benzthiophenes. J. Med. Chem. 2002, 45, 1399-1401.
12. Henke, B. R.; Consler, T. G.; Go, N.; Hale, R. L.; Hohman, D. R.; Jones, S. A.; Lu, A. T.; Moore, L. B.; Moore, J. T.; Orband-Miller, L. A.; Robinett, R. G.; Shearin, J.; Spearing, P. K.; Stewart, E. L.; Turnbull, P. S.; Weaver, S. L.; Williams, S. P.; Wisely, G. B.; Lambert, M. H. A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta. J. Med. Chem. 2002, 45, 5492-5505.
13. Wallace, O. B.; Richardson, T. I.; Dodge, J. A. Estrogen receptor modulators: Relationships of ligand structure, receptor affinity and functional activity. Curr. Top. Med. Chem. 2003, 3, 1663-1682.
14. Malamas, M. S.; Manas, E. S.; McDevitt, R. E.; Gunawan, I.; Zhang, X. B.; Collini, M. D.; Miller, C. P.; Dinh, T.; Henderson, R. A.; Keith, J. C., Jr.; Harris, H. A. Design and synthesis of aryl di-phenolic azoles as potent and selective estrogen receptor-b ligands. J. Med. Chem. 2004, 47, 5021-5040.
15. Harris, H. A.; Albert, L. M.; Leathurby, Y.; Malamas, M. S.; Mewshaw, R. E.; Miller, C. P.; Kharode, Y. P.; Marzolf, J.; Komm, B. S.; Winneker, R. C.; Frail, D. E.; Henderson, R. A.; Zhu, Y.; Keith, J. C., Jr. Evaluation of an estrogen receptor-beta agonist in animal models of human disease [comment]. Endocrinology 2003, 144, 4241-4249.
16. Kuiper, G.; Lemmen, J. G.; Carlsson, B.; Corton, J. C.; Safe, S. H.; Vandersaag, P. T.; Vanderburg, P.; Gustafsson, J. A. Interaction Of Estrogenic Chemicals and Phytoestrogens With Estrogen Receptor Beta. Endocrinology 1998, 139, 4252-4263.
17. Pike, A. C. W.; Brzozowski, A. M.; Hubbard, R. E.; Bonn, T.; Thorsell, A. G.; Engstrom, O.; Ljunggren, J.; Gustafsson, J. K.; 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.
18. Fang, H.; Tong, W.; Shi, L. M.; Blair, R.; Perkins, R.; Branham, W.; Hass, B. S.; Xie, Q.; Dial, S. L.; Moland, C. L.; Sheehan, D. M. Structure-Activity Relationships for a Large Diverse Set of Natural, Synthetic, and Environmental Estrogens. Chem. Res. Toxicol. 2001, 14, 280-294.
19. Ferte, J.; Kuhnel, J. M.; Chapuis, G.; Rolland, Y.; Lewin, G.; Schwaller, M. A. Flavonoid-related modulators of multidrug resistance: Synthesis, pharmacological activity, and structure-activity relationships. J. Med. Chem. 1999, 42, 478-489.
20. Kozerski, L.; Kamienski, B.; Kawecki, R.; Urbanczyk-Lipkowska, Z.; Bocian, W.; Bednarek, E.; Sitkowski, J.; Zakrzewska, K.; Nielsen, K. T.; Hansen, P. E. Solution and solid state 13C NMR and X-ray studies of genistein complexes with amines. Potential biological function of the C-7, C-5, and C-4′-OH groups. Org. Biomol. Chem. 2003, 1, 3578-3585.
21. Nishiyama, T.; Ogura, K.; Nakano, H.; Kahu, T.; Takahashi, E.; Ohkubo, Y.; Sekine, K.; Hiratsuka, A.; Kadota, S.; Watabe, T. Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab. Pharmacokinet. 2002, 17, 221-228.
22. Michalak, K.; Hendrich, A. B.; Wesolowska, O.; Pola, A. Compounds That Modulate Multidrug Resistance In Cancer Cells. Cell. Biol. Mol. Lett. 2001, 6, 362-368.
23. Mazurek, A. P.; Kozerski, L.; Sadlej, J.; Kawecki, R.; Bednarek, E.; Sitkowski, J.; Dobrowolski, J. C.; Maurin, J. K.; Biniecki, K.; Witowska, J.; Fiedor, P.; Pachecka, J. Genistein complexes with amines: Structure and properties. J. Chem. Soc., Perkin Trans 2: Phys. Org. Chem. 1998, 1223-1230.
24. Anstead, G. M.; Carlson, K. E.; Katzenellenbogen, J. A. The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 1997, 62, 268-303.
25. Dodge, J. A.; Glasebrook, A. L.; Lugar, C. W. Preparation of 5-(4-aminoalkoxybenzyl)-6-(4-hydroxyphenyl)-2-naphthols and analogues as antiestrogens. In Eur. Pat. Appl. (Eli Lilly and Company, USA). EP 895989 Al, 1999; 35 pp.
26. Manas, E. S.; Unwalla, R. J.; Xu, Z. B.; Malamas, M. S.; Miller, C. P.; Harris, H. A.; Hsiao, C.; Akopian, T.; Hum, W.-T.; Malakian, K.; Wolfrom, S.; Bapat, A.; Bhat, R. A.; Stahl, M. L.; Somers, W. S.; Alvarez, J. C. Structure-Based Design Of Estrogen Receptor-b Selective Ligands. J. Am. Chem. Soc. 2004, 726, 15106-15119.
27. Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J.-A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389, 753-758.
28. Warnmark, A.; Treuter, E.; Gustafsson, J. A.; Hubbard, R. E.; Brzozowski, A. M.; Pike, A. C. W. Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha. J. Biol. Chem. 2002, 277, 21862-21868.
29. Shiau, A. K.; Barstad, D.; Radek, J. T.; Meyers, M. J.; Nettles, K. W.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A.; Agard, D. A.; Greene, G. L. Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Nature Struct. Biol. 2002, 9, 359-364.
30. Harris, H. A.; Bapat, A. R.; Gonder, D. S.; Frail, D. E. The ligand binding profiles of estrogen receptors alpha and beta are species dependent. Steroids 2002, 67, 379-384.
31. Harris, H. A.; Katzenellenbogen, J. A.; Katzenellenbogen, B. S. Characterization of the biological roles of the estrogen receptors, ER alpha and ER beta, in estrogen target tissues in vivo through the use of an ER alpha-selective ligand. Endocrinology 2002, 143, 4172-4177.
32. Bodine, P. V. N.; Harris, H. A.; Lyttle, C. R.; Komm, B. S. Estrogenic effects of 7 alpha-methyl-17 alpha-ethynylestradiol: A newly discovered tibolone metabolite. Steroids 2002, 67, 681-686.
33. Miller, C. P.; Komm, B. S. Targeting the estrogen receptor with SERMs. Ann. Rep. Med. Chem. 2001, 36, 149-158.
34. Taurog, J. D.; Maika, S. D.; Satumtira, N.; Dorris, M. L.; McLean, I. L.; Yanagisawa, H.; Sayad, A.; Stagg, A. J.; Fox, G. M.; Le O'Brien, A.; Rehman, M.; Zhou, M.; Weiner, A. L.; Splawski, J. B.; Richardson, J. A.; Hammer, R. E. Inflammatory disease in HLA-B27 transgenic rats. Immunolog. Rev. 1999, 169, 209-223.
35. Zhang, Z. M.; Lundeen, S. G.; Zhu, Y.; Carver, J. M.; Winneker, R. C. In vitro characterization of trimegestone: A new potent and selective progestin. Steroids 2000, 65, 637-643.
36. Heery, D. M.; Hoare, S.; Hussain, S.; Parker, M. G.; Sheppard, H. Core LXXLL motif sequences in CREB-binding protein, SRC1, and RIP140 define affinity and selectivity for steroid and retinoid receptors. J Biol. Chem. 2001, 276, 6695-6702.
37. Wong, C. W.; Komm, B.; Cheskis, B. J. Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands. Biochemistry 2001, 40, 6756-6765.
38. McPherson, A., Jr. The growth and preliminary investigation of protein and nucleic acid crystals for X-ray diffraction analysis. Methods. Biochem. Anal. 1976, 23, 249-345.
39. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods. Enzymol. 1994, 276, 307-326.
40. Bailey, S. The CCP4 suite: Programs for protein crystallography. Acta Crystallogr., Sect. D 1994, 50, 760-763.
41. Tanenbaum, D. M.; Wang, Y.; Williams, S. P.; Sigler, P. B. Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 5998-6003.
42. Brunger, A. Crystallography and NMR system: A new sofware suite for macromolecular structure determination. Acta Crystallogr., Sect. D 1998, 55, 941-944.
43. McMartin, C.; Bohacek, R. S. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput.-Aided Mol. Des. 1997, 11, 333-344.
44. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 1993, 26, 283-291.