title: Synthesis and biological evaluation of second-generation tropanol-based androgen receptor modulators.
abstract: To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
authors: Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of Gothenburg , SE-41296 Gothenburg, Sweden.
authors: Henrik
authors: H
authors: Sundén
authors: Mareike C
authors: MC
authors: Holland
authors: Pekka K
authors: PK
authors: Poutiainen
authors: Tiina
authors: T
authors: Jääskeläinen
authors: Juha T
authors: JT
authors: Pulkkinen
authors: Jorma J
authors: JJ
authors: Palvimo
authors: Roger
authors: R
authors: Olsson
mesh_terms: D059002:Androgen Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D059002:Androgen Receptor Antagonists; D008024:Ligands; D011944:Receptors, Androgen; D014326:Tropanes