[2.2.1]-Bicyclic sultams as potent androgen receptor antagonists

Bioorg Med Chem Lett. 2016 Dec 1;26(23):5707-5711. doi: 10.1016/j.bmcl.2016.10.059. Epub 2016 Oct 21.

Abstract

This letter describes the discovery, synthesis, SAR, and biological activity of [2.2.1]-bicyclic sultams as potent antagonists of the androgen receptor. Optimization of the series led to the identification of compound 25, which displayed robust pharmacodynamic effects in rats after oral dosing.

Keywords: Androgen receptor antagonist; Cancer; Nuclear hormone receptor; Pharmacokinetics and pharmacodynamics.

MeSH terms

  • Administration, Oral
  • Androgen Receptor Antagonists / chemistry*
  • Androgen Receptor Antagonists / pharmacokinetics
  • Androgen Receptor Antagonists / pharmacology*
  • Animals
  • Bridged Bicyclo Compounds / administration & dosage
  • Bridged Bicyclo Compounds / chemistry*
  • Bridged Bicyclo Compounds / pharmacokinetics
  • Bridged Bicyclo Compounds / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Models, Molecular
  • Naphthalenesulfonates / administration & dosage
  • Naphthalenesulfonates / chemistry*
  • Naphthalenesulfonates / pharmacokinetics
  • Naphthalenesulfonates / pharmacology*
  • Rats
  • Receptors, Androgen / metabolism
  • Structure-Activity Relationship

Substances

  • Androgen Receptor Antagonists
  • Bridged Bicyclo Compounds
  • Naphthalenesulfonates
  • Receptors, Androgen
  • naphthosultone