(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I)

Chem Pharm Bull (Tokyo). 1998 Nov;46(11):1683-7. doi: 10.1248/cpb.46.1683.

Abstract

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Animals
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Male
  • Prostate / drug effects
  • Prostate / enzymology
  • Rats
  • Rats, Wistar
  • Spectroscopy, Fourier Transform Infrared

Substances

  • 5-alpha Reductase Inhibitors
  • Carboxylic Acids
  • Enzyme Inhibitors
  • Indoles