Diarylpropionitrile (DPN) enantiomers: Synthesis and evaluation of estrogen receptor β-selective ligands

Journal of Medicinal Chemistry

Volumn 55, Issue 1, 2012, Pages 528-537

  Carroll, Vincent M ^a   Jeyakumar, M ^a   Carlson, Kathryn E ^a   Katzenellenbogen, John A ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIARYLPROPIONITRILE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; LIGAND;

ARTICLE; BINDING AFFINITY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG SCREENING; DRUG SYNTHESIS; ENANTIOMER; ENANTIOSELECTIVITY; HUMAN; HUMAN CELL; IN VITRO STUDY; ISOMER; LIGAND BINDING;

CELL LINE, TUMOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMANS; LIGANDS; MOLECULAR CONFORMATION; NITRILES; NUCLEAR RECEPTOR COACTIVATOR 3; PROTEIN BINDING; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTIONAL ACTIVATION; TRANSFECTION;

EID: 84855860349     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201436k     Document Type: Article

References (41)

1. McDonnell, D. P. The Molecular Pharmacology of SERMs Trends Endocrinol. Metab. 1999, 10, 301-311
2. McDonnell, D. P. Selective estrogen receptor modulators (SERMs): a first step in the development of perfect hormone replacement therapy regimen J. Soc. Gynecol. Invest. 2000, 7, S10-S15
3. Smith, C. L.; OMalley, B. W. Coregulator function: a key to understanding tissue specificity of selective receptor modulators Endocr. Rev. 2004, 25, 45-71
4. Kuiper, G. G.; Enmark, E.; Pelto-Huikko, M.; Nilsson, S.; Gustafsson, J. A. Cloning of a novel receptor expressed in rat prostate and ovary Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 5925-5930
5. Kuiper, G. G.; Gustafsson, J. A. The novel estrogen receptor-beta subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens FEBS Lett. 1997, 410, 87-90
6. Mosselman, S.; Polman, J.; Dijkema, R. ER beta: identification and characterization of a novel human estrogen receptor FEBS Lett. 1996, 392, 49-53
7. Lindberg, M. K.; Moverare, S.; Skrtic, S.; Gao, H.; Dahlman-Wright, K.; Gustafsson, J. A.; Ohlsson, C. Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice Mol. Endocrinol. 2003, 17, 203-208
8. Nilsson, S.; Gustafsson, J. A. Estrogen receptors: therapies targeted to receptor subtypes Clin. Pharmacol. Ther. 2011, 89, 44-55
9. Zhao, C.; Dahlman-Wright, K.; Gustafsson, J. A. Estrogen receptor beta: an overview and update Nucl. Recept. Signaling 2008, 6, e003
10. Harris, H. A. Estrogen receptor-beta: recent lessons from in vivo studies Mol. Endocrinol. 2007, 21, 1-13
11. Minutolo, F.; Macchia, M.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Estrogen receptor beta ligands: recent advances and biomedical applications Med. Res. Rev. 2011, 31, 364-442
12. 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
13. Sun, J.; Meyers, M. J.; Fink, B. E.; Rajendran, R.; Katzenellenbogen, J. A.; Katzenellenbogen, B. S. Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-alpha or estrogen receptor-beta Endocrinology 1999, 140, 800-804
14. Sun, J.; Baudry, J.; Katzenellenbogen, J. A.; Katzenellenbogen, B. S. Molecular basis for the subtype discrimination of the estrogen receptor-beta-selective ligand, diarylpropionitrile Mol. Endocrinol. 2003, 17, 247-258
15. Weiser, M. J.; Wu, T. J.; Handa, R. J. Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R-and S -enantiomers on behavior and hormonal response to stress Endocrinology 2009, 150, 1817-1825
16. 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
17. Evans, D. A. Studies in asymmetric synthesis. The development of practical chiral enolate synthons Aldrichimica Acta 1982, 15, 23-32
18. Prashad, M.; Kim, H.-Y.; Har, D.; Repic, O.; Blacklock, T. J. A convenient and practical method for N -acylation of 2-oxazolidinone chiral auxiliaries with acids Tetrahedron Lett. 1998, 39, 9369-9372
19. Heemstra, J. M.; Kerrigan, S. A.; Doerge, D. R.; Helferich, W. G.; Boulanger, W. A. Total Synthesis of (S)-Equol Org. Lett. 2006, 8, 5441-5443
20. Stang, E. M.; Christina, W. M. Total synthesis and study of 6-deoxyerythronolide B by late-stage C-H oxidation Nature Chem. 2009, 1, 547-551
21. Taylor, J. G.; Li, X.; Oberthuer, M.; Zhu, W.; Kahne, D. E. The Total Synthesis of Moenomycin A J. Am. Chem. Soc. 2006, 128, 15084-15085
22. Barbosa, A. J. M.; Brunette, S. R.; Hickey, E. R.; Lawlor, M. D.; Tschantz, M. A. Preparation of pyrimidine derivatives useful as inhibitors of PKC-theta for treating various diseases. WO2007076247A1, 2007.
23. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Stereoselective amination of chiral enolates. A new approach to the asymmetric synthesis of α-hydrazino and α-amino acid derivatives J. Am. Chem. Soc. 1986, 108, 6395-6397
24. Evans, D. A.; Ennis, M. D.; Mathre, D. J. Asymmetric alkylation reactions of chiral imide enolates. A practical approach to the enantioselective synthesis of α-substituted carboxylic acid derivatives J. Am. Chem. Soc. 1982, 104, 1737-1739
25. Evans, D. A.; Kaldor, S. W.; Jones, T. K.; Clardy, J.; Stout, T. J. Total synthesis of the macrolide antibiotic cytovaricin J. Am. Chem. Soc. 1990, 112, 7001-7031
26. Carlson, K. E.; Choi, I.; Gee, A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction Biochemistry 1997, 36, 14897-14905
27. Katzenellenbogen, J. A.; Johnson, H. J., Jr.; Carlson, K. E. Studies on the uterine, cytoplasmic estrogen binding protein. Thermal stability and ligand dissociation rate. An assay of empty and filled sites by exchange Biochemistry 1973, 12, 4092-4099
28. Bramlett, K. S.; Wu, Y.; Burris, T. P. Ligands specify coactivator nuclear receptor (NR) box affinity for estrogen receptor subtypes Mol. Endocrinol. 2001, 15, 909-922
29. Iannone, M. A.; Simmons, C. A.; Kadwell, S. H.; Svoboda, D. L.; Vanderwall, D. E.; Deng, S. J.; Consler, T. G.; Shearin, J.; Gray, J. G.; Pearce, K. H. Correlation between in vitro peptide binding profiles and cellular activities for estrogen receptor-modulating compounds Mol. Endocrinol. 2004, 18, 1064-1081
30. Liu, J.; Knappenberger, K. S.; Kack, H.; Andersson, G.; Nilsson, E.; Dartsch, C.; Scott, C. W. A homogeneous in vitro functional assay for estrogen receptors: coactivator recruitment Mol. Endocrinol. 2003, 17, 346-355
31. Jeyakumar, M.; Carlson, K. E.; Gunther, J. R.; Katzenellenbogen, J. A. Exploration of dimensions of estrogen potency: parsing ligand binding and coactivator binding affinities J. Biol. Chem. 2011, 286, 12971-12982
32. Gunther, J. R.; Du, Y.; Rhoden, E.; Lewis, I.; Revennaugh, B.; Moore, T. W.; Kim, S. H.; Dingledine, R.; Fu, H.; Katzenellenbogen, J. A. A set of time-resolved fluorescence resonance energy transfer assays for the discovery of inhibitors of estrogen receptor-coactivator binding J. Biomol. Screening 2009, 14, 181-193
33. Jeyakumar, M.; Webb, P.; Baxter, J. D.; Scanlan, T. S.; Katzenellenbogen, J. A. Quantification of ligand-regulated nuclear receptor corepressor and coactivator binding, key interactions determining ligand potency and efficacy for the thyroid hormone receptor Biochemistry 2008, 47, 7465-7476
34. Krey, G.; Braissant, O.; LHorset, F.; Kalkhoven, E.; Perroud, M.; Parker, M. G.; Wahli, W. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay Mol. Endocrinol. 1997, 11, 779-791
35. Couse, J. F.; Korach, K. S. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr. Rev. 1999, 20, 358-417
36. Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Nishiguchi, G.; Carlson, K.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists J. Med. Chem. 2000, 43, 4934-4947
37. Pike, A. C.; Brzozowski, A. M.; Hubbard, R. E.; Bonn, T.; Thorsell, A. G.; Engstrom, O.; Ljunggren, J.; Gustafsson, J. A.; 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
38. Richardson, T. I.; Dodge, J. A.; Wang, Y.; Durbin, J. D.; Krishnan, V.; Norman, B. H. Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: Combined A- and C-ring structure-activity relationship studies Bioorg. Med. Chem. Lett. 2007, 17, 5563-5566
39. Saijo, K.; Collier, J. G.; Li, A. C.; Katzenellenbogen, J. A.; Glass, C. K. An ADIOL-ERbeta-CtBP transrepression pathway negatively regulates microglia-mediated inflammation Cell 2011, 145, 584-595
40. Kim, S. H.; Tamrazi, A.; Carlson, K. E.; Daniels, J. R.; Lee, I. Y.; Katzenellenbogen, J. A. Estrogen receptor microarrays: subtype-selective ligand binding J. Am. Chem. Soc. 2004, 126, 4754-4755
41. Zhou, H. B.; Carlson, K. E.; Stossi, F.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Analogs of methyl-piperidinopyrazole (MPP): antiestrogens with estrogen receptor alpha selective activity Bioorg. Med. Chem. Lett. 2009, 19, 108-110