Abstract |
We have investigated halogen-substituted non-steroidal estrogens with selective binding affinity for the estrogen receptor beta ( ERbeta that might be used for imaging the levels of this ER-subtype in breast tumors by positron emission tomography (PET). Based on diarylpropionitrile ( DPN, 1a), a compound previously reported that has a 72-fold binding selectivity for ERbeta, we developed a series of DPN analogs having methyl-, hydroxyl-, and halogen substituents, including fluoroethyl and fluoropropyl groups. In competitive radiometric binding assays with [(3)H] estradiol, all of these DPN analogs showed high ERbeta/ ERalpha selectivity; while the selectivity varied, in some cases it reached nearly 300-fold (RBA: ERalpha, 0.023%; ERbeta, 6.25%). The absolute ERbeta binding affinities, however, were not sufficient to merit further consideration for developing these ligands as PET imaging agents.
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Authors | Byung Seok Moon, Kathryn E Carlson, John A Katzenellenbogen, Tae Hyun Choi, Dae Yoon Chi, Jung Young Kim, Gi Jeong Cheon, Hun Yeong Koh, Kyo Chul Lee, Gwangil An |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 17
Issue 9
Pg. 3479-88
(May 01 2009)
ISSN: 1464-3391 [Electronic] England |
PMID | 19359182
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2,3-bis(4-hydroxyphenyl)-propionitrile
- Estrogen Receptor beta
- Fluorine Radioisotopes
- Ligands
- Nitriles
- Propionates
- Radiopharmaceuticals
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Topics |
- Binding, Competitive
- Estrogen Receptor beta
(chemistry, metabolism)
- Fluorine Radioisotopes
(chemistry)
- Humans
- Kinetics
- Ligands
- Nitriles
(chemical synthesis, chemistry)
- Positron-Emission Tomography
- Propionates
(chemical synthesis, chemistry)
- Protein Binding
- Radiopharmaceuticals
(chemical synthesis, chemistry)
- Structure-Activity Relationship
- Substrate Specificity
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