Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor

Bioorg Med Chem Lett. 2011 Jan 1;21(1):475-8. doi: 10.1016/j.bmcl.2010.10.112. Epub 2010 Oct 28.

Abstract

Finasteride and epristeride both inhibit 5α-reductase with high potency via competitive and non-competitive mechanism, respectively. A new hybrid of finasteride and epristeride was designed as a new 5α-reductase inhibitor based on combination principles in medicinal chemistry. Human 5β-reductase was chosen as a plausible surrogate of 5α-reductase type II and the results indicate that although the hybrid compound possesses the main bulk of epristeride, its inhibitory mechanism is same as of finasteride. The hybrid turned out to be a potent 5α-reductase inhibitor in low IC(50) ranges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / chemistry*
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • 5-alpha Reductase Inhibitors / chemical synthesis
  • 5-alpha Reductase Inhibitors / chemistry*
  • 5-alpha Reductase Inhibitors / pharmacology
  • Androstadienes / chemistry*
  • Binding Sites
  • Catalytic Domain
  • Computer Simulation
  • Drug Evaluation, Preclinical
  • Finasteride / analogs & derivatives*
  • Finasteride / chemical synthesis
  • Finasteride / chemistry
  • Finasteride / pharmacology
  • Humans

Substances

  • 5-alpha Reductase Inhibitors
  • Androstadienes
  • epristeride
  • Finasteride
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase