title: Study of E/Z isomerization in a series of novel non-ligand binding pocket androgen receptor antagonists.
abstract: We report the conformational analysis of a series of 3-hydroxy-N'-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure-activity relationship analysis.
authors.affiliation: Molecular Design Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. blancof@tcd.ie
authors.forename: Fernando
authors.initials: F
authors.lastname: Blanco
authors.forename: Billy
authors.initials: B
authors.lastname: Egan
authors.forename: Laura
authors.initials: L
authors.lastname: Caboni
authors.forename: José
authors.initials: J
authors.lastname: Elguero
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Thomas
authors.initials: T
authors.lastname: McCabe
authors.forename: Darren
authors.initials: D
authors.lastname: Fayne
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Meegan
authors.forename: David G
authors.initials: DG
authors.lastname: Lloyd
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D007536:Isomerism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D011487:Protein Conformation; D011944:Receptors, Androgen / Q000737:chemistry*
chemical_list: D000726:Androgen Antagonists; D008024:Ligands; D011944:Receptors, Androgen