2-Arylindoles as gonadotropin releasing hormone (GnRH) antagonists: optimization of the tryptamine side chain

Bioorg Med Chem Lett. 2002 Mar 11;12(5):827-32. doi: 10.1016/s0960-894x(02)00026-4.

Abstract

A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Buserelin / metabolism
  • Fertility Agents, Female / antagonists & inhibitors*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Humans
  • Indoles / administration & dosage
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inositol Phosphates / metabolism
  • Luteinizing Hormone / metabolism
  • Male
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Tryptamines / chemistry*

Substances

  • Fertility Agents, Female
  • Indoles
  • Inositol Phosphates
  • Quinolines
  • Tryptamines
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Buserelin