Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes.
| Autor: | Bertini S; Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy., De Cupertinis A, Granchi C, Bargagli B, Tuccinardi T, Martinelli A, Macchia M, Gunther JR, Carlson KE, Katzenellenbogen JA, Minutolo F |
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| Jazyk: | angličtina |
| Zdroj: | European journal of medicinal chemistry [Eur J Med Chem] 2011 Jun; Vol. 46 (6), pp. 2453-62. Date of Electronic Publication: 2011 Mar 23. |
| DOI: | 10.1016/j.ejmech.2011.03.030 |
| Abstrakt: | In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor β (ERβ) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERβ-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERβ-subtype selectivity. Both compounds show a potent full agonist character on ERβ (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a β/α transcription potency ratio 50-fold higher than that of estradiol. (Copyright © 2011 Elsevier Masson SAS. All rights reserved.) |
| Databáze: | MEDLINE |
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