SAR based design of nicotinamides as a novel class of androgen receptor antagonists for prostate cancer

J Med Chem. 2013 Apr 25;56(8):3414-8. doi: 10.1021/jm3014103. Epub 2013 Apr 5.


Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement. AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgen Receptor Antagonists / pharmacology*
  • Androgen Receptor Antagonists / therapeutic use
  • Cell Line, Tumor
  • Drug Design
  • Humans
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / pharmacology
  • Male
  • Niacinamide / analogs & derivatives
  • Niacinamide / pharmacology
  • Prostatic Neoplasms / drug therapy*
  • Receptors, Androgen / drug effects*
  • Structure-Activity Relationship


  • 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide
  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Isoquinolines
  • Receptors, Androgen
  • Niacinamide