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http://dx.doi.org/10.5012/bkcs.2008.29.6.1107

Synthesis and Evaluation of Estrogen Receptor β -Selective Ligands: Fluoroalkylated Indazole Estrogens  

Moon, Byung-Seok (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS))
Katzenellenbogen, John A. (Department of Chemistry, University of Illinois)
Cheon, Gi-Jeong (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS))
Chi, Dae-Yoon (Department of Chemistry, Inha University)
Lee, Kyo-Chul (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS))
An, Gwang-Il (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS))
Publication Information
Bulletin of the Korean Chemical Society / v.29, no.6, 2008 , pp. 1107-1114 More about this Journal
Abstract
It is important to identify selective ligands for the estrogen receptor subtypes ER$\alpha$ or ER$\beta$ to evaluate them as pharmaceutical targets in breast cancer. To develop ER$\beta$-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ER$\alpha$ vs ER$\beta$. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ER$\beta$/ER$\alpha$ selectivity, respectively. However, their binding affinities to ER$\alpha$ and ER$\beta$ were very low.
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1 Green, S.; Walter, P.; Kumar, V.; Krust, A.; Bornert, J. M.; Argos, P.; Chambon, P. Nature 1986, 320, 134   DOI   ScienceOn
2 Ritzen, E. M.; Nilsson, O.; Holst, M.; Savendahl, L.; Wroblewski, J. J. Steroid Biochem. Mol. Biol. 2000, 74, 383   DOI   ScienceOn
3 Tsai, M. J.; O'Malley, B. W. Annu. Rev. Biochem. 1994, 63, 451   DOI   ScienceOn
4 Mortensen, D. S.; Rodriguez, A. L.; Carlson, K. E.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2001, 44, 3838   DOI   ScienceOn
5 Barlaam, B.; Bernstein, P.; Dantzman, C.; Warwick, P. An 2002:504768, WO02/051821, 2002
6 Barlaam, B.; Dock, S.; Folmer, J. An 2002:449659, WO02/046168, 2002
7 Carlson, K. E.; Choi, I.; Gee, A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Biochemistry 1997, 36, 14897   DOI   ScienceOn
8 Boovanahalli, S. K.; Kim, D. W.; Chi, D. Y. J. Org. Chem. 2004, 69, 3340   DOI   ScienceOn
9 Song, J. J.; Yee, N. K. Org. Lett. 2000, 2, 519   DOI   ScienceOn
10 Yoo, J.; Dence, C. S.; Sharp, T. L.; Katzenellenbogen, J. A.; Welch, M. J. J. Med. Chem. 2005, 48, 6366   DOI   ScienceOn
11 Angelis, M. D.; Stossi, F.; Carlson, K. A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2005, 48, 1132   DOI   ScienceOn
12 Nilsson, S.; Makela, S.; Treuter, E.; Tujague, M.; Thomsen, J.; Andersson, G.; Enmark, E.; Pettersson, K.; Warner, M.; Gustafsson, J. A. Physiological Rev. 2001, 81, 1535   DOI
13 Malamas, M. S.; Manas, E. S.; McDevitt, R. E.; Gunawan, I.; Xu, Z. B.; Collini, M. D.; Miller, C. P.; Dinh, T.; Henderson, R. A.; Keith, J. C., Jr.; Harris, H. A. J. Med. Chem. 2004, 47, 5021   DOI   ScienceOn
14 Muthyala, R. S.; Sheng, S.; Carlson, K. E.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2003, 46, 1589   DOI   ScienceOn
15 Seo, J. W.; Comninos, J. S.; Chi, D. Y.; Kim, D. W.; Carlson, K. E.; Katzenellenbogen, J. A. J. Med. Chem. 2006, 49, 2496   DOI   ScienceOn
16 Pettersson, K.; Gustafsson, J. A. Annu. Rev. Physiol 2001, 63, 165   DOI   ScienceOn
17 Roger, P.; Sahla, M. E.; Makela, S.; Gustafsson, J. A.; Baldet, P.; Rochefort, H. Cancer Res. 2001, 61, 2537
18 Kuiper, G. G. J. M.; Carlsson, B.; Grandien, K.; Enmark, E.; Haeggblad, J.; Nilsson, S.; Gustafsson, J.-A. Endocrinology 1997, 138, 863   DOI   ScienceOn
19 Kuiper, G. G.; Gustafsson, J. A. FEBS Lett. 1997, 410, 87   DOI   ScienceOn
20 Weihua, Z.; Andersson, S.; Cheng, G.; Simpson Evan, R.; Warner, M.; Gustafsson, J.-A. FEBS Lett. 2003, 546, 17   DOI   ScienceOn
21 Mosselman, S.; Polman, J.; Dijkema, R. FEBS Lett. 1996, 392, 49   DOI   ScienceOn
22 Kuiper, G. G. J. M.; Enmark, E.; Pelto-Huikko, M.; Nilsson, S.; Gustafsson, J. A. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 5925   DOI
23 Kim, D. W.; Ahn, D.-S.; Oh, Y.-H.; Lee, S.; Kil, H. S.; Oh, S. J.; Lee, S. J.; Kim, J. S.; Ryu, J. S.; Moon, D. H.; Chi, D. Y. J. Am. Chem. Soc. 2006, 128, 16393
24 Gao, H.; Katzenellenbogen, J. A.; Garg, R.; Hansch, C. Chem. Rev. 1999, 99, 723   DOI   ScienceOn
25 Abney, T. O. Mol. Androl. 1992, 4, 281
26 Meyers, M. J.; Sun, J.; Carlson, K. E.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 1999, 42, 2456   DOI   ScienceOn
27 Mosselman, S.; Polman, J.; Dijkema, R. FEBS Lett. 1996, 392, 49   DOI   ScienceOn
28 Toran-Allerand, C. D. J. Steroid Biochem. Mol. Biol. 1996, 56, 169   DOI   ScienceOn
29 Kuiper, G. G. J. M.; Carlquist, M.; Gustafsson, J.-A. Sci. Med. (Philadelphia) 1998, 5, 36
30 Omoto, Y.; Kobayashi, S.; Inoue, S.; Ogawa, S.; Toyama, T.; Yamashita, H.; Muramatsu, M.; Gustafsson, J. A.; Iwase, H. Eur. J. Cancer 2002, 38, 380   DOI   ScienceOn
31 Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engström, O.; Ohman, L.; Greene, G. L.; Gustafsson, J.- Å.; Carlquist, M. Nature 1997, 389, 753   DOI   ScienceOn
32 Meyers, M. J.; Sun, J.; Carlson, K. E.; Marriner, G. A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2001, 44, 4230   DOI   ScienceOn
33 Pike, A. C.; Brzozowski, A. M.; Hubbard, R. E.; Bonn, T.; Thorsell, A. G.; Engstrom, O.; Ljunggren, J.; Gustafsson, J.; Carlquist, M. EMBO J. 1999, 18, 4608   DOI   ScienceOn
34 Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Nishiguchi, G.; Carlson, K. E.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2000, 43, 4934   DOI   ScienceOn
35 Schopfer, U.; Schoeffter, P.; Bischoff, S. F.; Nozulak, J.; Feuerbach, D.; Floersheim, P. J. Med. Chem. 2002, 45, 1399   DOI   ScienceOn
36 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. Endocrinology 2003, 144, 4241   DOI   ScienceOn
37 Vijaykumar, D.; Al-Qahtani, M. H.; Welch, M. J.; Katzenellenbogen, J. A. Nucl. Med. Biol. 2003, 30, 397   DOI   ScienceOn