Synthesis and biological evaluation of second-generation tropanol-based androgen receptor modulators

J Med Chem. 2015 Feb 12;58(3):1569-74. doi: 10.1021/jm501995n. Epub 2015 Feb 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Receptor Antagonists / chemical synthesis
  • Androgen Receptor Antagonists / chemistry
  • Androgen Receptor Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Molecular Structure
  • Mutation
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Structure-Activity Relationship
  • Tropanes / chemical synthesis
  • Tropanes / chemistry
  • Tropanes / pharmacology*


  • Androgen Receptor Antagonists
  • Ligands
  • Receptors, Androgen
  • Tropanes