title: Design and synthesis of an array of selective androgen receptor modulators.
abstract: We describe the design, using shape comparison and fast docking computer algorithms, and rapid parallel synthesis of a 1300 member array based on GSK7721, a 4-aminobenzonitrile androgen receptor (AR) antagonist identified by focused screening of the GSK compound collection. The array yielded 352 submicromolar and 17 subnanomolar AR agonists as measured by a cell-based reporter gene functional assay. The rapid synthesis of a large number of active compounds provided valuable information in the optimization of AR modulators, which may be useful in treating androgen deficiency in aging males.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. ryan.p.trump@gsk.com
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Trump
authors.forename: Jean-Baptiste E
authors.initials: JB
authors.lastname: Blanc
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Stewart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brown
authors.forename: Matilde
authors.initials: M
authors.lastname: Caivano
authors.forename: David W
authors.initials: DW
authors.lastname: Gray
authors.forename: William J
authors.initials: WJ
authors.lastname: Hoekstra
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Willson
authors.forename: Bajin
authors.initials: B
authors.lastname: Han
authors.forename: Philip
authors.initials: P
authors.lastname: Turnbull
mesh_terms: D000465:Algorithms; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D000882:Haplorhini; D009682:Magnetic Resonance Spectroscopy; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
chemical_list: D059002:Androgen Receptor Antagonists; D000728:Androgens; D009570:Nitriles; C045271:4-aminobenzonitrile