title: Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.
abstract: After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure-activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific SAR response, absence of a readily oxidized sulfur atom, low molecular weight, reduced number of flexible bonds and polar surface area, and drug-likeness score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl cells to qualify as a new lead structure for prostate cancer drug development.
authors: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors: James K
authors: JK
authors: Johnson
authors: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors: Erin M
authors: EM
authors: Skoda
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Jianhua
authors: J
authors: Zhou
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Erica
authors: E
authors: Parrinello
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Dan
authors: D
authors: Wang
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Katherine
authors: K
authors: O'Malley
authors: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors: Benjamin R
authors: BR
authors: Eyer
authors: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors: Mustafa
authors: M
authors: Kazancioglu
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Kurtis
authors: K
authors: Eisermann
authors: Department of Pharmaceutical Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania 15261, United States.
authors: Paul A
authors: PA
authors: Johnston
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Joel B
authors: JB
authors: Nelson
authors: Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15232, United States.
authors: Zhou
authors: Z
authors: Wang
authors: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.
authors: Peter
authors: P
authors: Wipf
keywords: Androgen receptor; CRPC; advanced prostate cancer; isoxazoles; luciferase assay; thioether isostere