title: Ring nitrogen-substituted non-steroidal estrogens: pyridine and pyrimidine analogs of the phenol in deoxyhexestrol experience resonance constraints on preferred ligand conformation.
abstract: To develop compounds selective for estrogen receptor beta (ERbeta), we substituted hydroxypyridine and pyrimidine heteroaryl groups for the characteristic phenol ring of non-steroidal estrogens. The unexpectedly low affinity showed by some of these compounds is ascribed, in part, to a resonance-enforced conformational constraint that prevents their optimal accommodation in the ER ligand binding pocket.
authors.affiliation: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Meri
authors.initials: M
authors.lastname: De Angelis
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004968:Estrogens, Non-Steroidal; D008024:Ligands; D010636:Phenols; D011725:Pyridines; D011743:Pyrimidines