Parallel solid-phase synthesis of a model library of 7alpha-alkylamide estradiol derivatives as potential estrogen receptor antagonists

Bioorg Med Chem Lett. 1999 Oct 4;9(19):2827-32. doi: 10.1016/s0960-894x(99)00487-4.

Abstract

The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first level of diversity. Subsequent deprotection of the Fmoc followed by a second acylation with five activated carboxylic acids produced, after photocleavage, a model library of twenty antiestrogen-related 7alpha-alkylamide estradiol derivatives in acceptable overall yields and very good purities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Breast Neoplasms
  • Cell Division / drug effects
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry
  • Estradiol / pharmacology
  • Estrogen Receptor Modulators / chemical synthesis*
  • Estrogen Receptor Modulators / pharmacology
  • Humans
  • Molecular Structure
  • Polyunsaturated Alkamides
  • Receptors, Estrogen / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Amides
  • Estrogen Receptor Modulators
  • Polyunsaturated Alkamides
  • Receptors, Estrogen
  • Estradiol
  • ICI 164384