Salicylaldoxime moiety as a phenolic "A-Ring" substitute in estrogen receptor ligands.
The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the ER. The OH of the oxime function appears to mimic the phenolic OH present in more "classical" ER ligands because the binding reduced when the oxime OH is methylated (2) or absent (3).
Minutolo
F
F
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Bertini
S
S
Papi
C
C
Carlson
K E
KE
Katzenellenbogen
J A
JA
Macchia
M
M
D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D011869:Radioligand Assay; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D010091:Oximes; D010636:Phenols; D011960:Receptors, Estrogen; D012459:Salicylates; C005704:salicylaldoxime