7-Substituted 2-phenyl-benzofurans as ERβ selective ligands

Abstract A series of 2-(4-hydroxy-phenyl)-benzofuran-5-ols with relatively lipophilic groups in the 7-position of the benzofuran was prepared and the affinity and selectivity for ERβ was measured. Many of the analogues were found to be potent and selective ERβ ligands. Additional modifications at the benzofuran 4-position as well as at the 3′-position of the 2-phenyl group were found to further increase selectivity. Such modifications led to compounds with 100-fold selectivity for ERβ.

[1]  J. Wroblewski,et al.  Estrogens and human growth , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[2]  康文 沢田.  Kinetic Analysis of Cerebrovascular Transport Based on the Multiple Indicator Dilution Method , 1988 .

[3]  B. Katzenellenbogen,et al.  Characterization of the Biological Roles of the Estrogen Receptors, ERα and ERβ, in Estrogen Target Tissues in Vivo through the Use of an ERα-Selective Ligand , 2002 .

[4]  G. Lewin,et al.  Flavonoid-related modulators of multidrug resistance: synthesis, pharmacological activity, and structure-activity relationships. , 1999, Journal of medicinal chemistry.

[5]  H. Harris,et al.  The ligand binding profiles of estrogen receptors α and β are species dependent , 2002, Steroids.

[6]  U. Schopfer,et al.  Toward selective ERbeta agonists for central nervous system disorders: synthesis and characterization of aryl benzthiophenes. , 2002, Journal of medicinal chemistry.

[7]  S. Kadota,et al.  Sulfation of environmental estrogens by cytosolic human sulfotransferases. , 2002, Drug metabolism and pharmacokinetics.

[8]  K E Carlson,et al.  Estrogen receptor subtype-selective ligands: asymmetric synthesis and biological evaluation of cis- and trans-5,11-dialkyl- 5,6,11, 12-tetrahydrochrysenes. , 1999, Journal of medicinal chemistry.

[9]  B. Katzenellenbogen,et al.  Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. , 2001, Journal of medicinal chemistry.

[10]  K. Zakrzewska,et al.  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 , 2003 .

[11]  G. Evano,et al.  A convergent synthesis of the macrocyclic core of cytotrienins: application of RCM for macrocyclization. , 2004, Organic letters.

[12]  J. Gustafsson,et al.  Cloning of a novel receptor expressed in rat prostate and ovary. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Komm,et al.  Evaluation of an Estrogen Receptor-β Agonist in Animal Models of Human Disease , 2003 .

[14]  Eric S Manas,et al.  ERβ Ligands. Part 1: The discovery of ERβ selective ligands which embrace the 4-hydroxy-biphenyl template , 2003 .

[15]  M Carlquist,et al.  Structure of the ligand‐binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist , 1999, The EMBO journal.

[16]  Eric S Manas,et al.  ERbeta ligands. Part 2: Synthesis and structure-activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivatives. , 2004, Bioorganic & medicinal chemistry.

[17]  G. Kuiper,et al.  Estrogen receptor and the SERM concept , 1999, Journal of endocrinological investigation.