Potent estrogen receptor ligands based on bisphenols with a globular hydrophobic core.
Candidate estrogen receptor (ER) ligands with two phenolic residues on a three-dimensional hydrophobic core structure (carborane, bicyclo[2.2.2]octene, or adamantane) were synthesized and biologically evaluated. The biological properties of the ligands were markedly dependent on the nature of the hydrophobic core structure. Bis(4-hydroxyphenyl)-o-carborane (6) was a partial agonist/antagonist for ER. 1,2-Bis(4-hydroxyphenyl)bicyclo[2.2.2]octene (10) exhibited potent agonist activity for ER, even though the two phenolic groups are located similarly to those of 6.
Endo
Yasuyuki
Y
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Komatsushima, Aoba-ku, Sendai, Japan. yendo@tohoku-pharma.ac.jp
Yoshimi
Tomohiro
T
Ohta
Kiminori
K
Suzuki
Tomoharu
T
Ohta
Shigeru
S
D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D001896:Boron Compounds; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D010636:Phenols; D011960:Receptors, Estrogen; D000218:Adamantane