Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor

Bioorg Med Chem Lett. 2000 Feb 21;10(4):399-402. doi: 10.1016/s0960-894x(00)00015-9.

Abstract

1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine (NNC 45-0095) is a novel compound which represents the parent pharmacophore structure of a series of pyrrolo[2,1,5-cd]indolizine derivatives with mixed estrogen agonist/antagonist properties. NNC 45-0095 binds with high affinity to the estrogen receptor (IC50=9.5 nM) and exhibits full protection of bone loss in the ovariectomized mouse model for post-menopausal osteoporosis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Assay
  • Bone Density / drug effects
  • Cytosol / chemistry
  • Cytosol / metabolism
  • Disease Models, Animal
  • Drug Evaluation
  • Estradiol / metabolism
  • Estrogen Replacement Therapy
  • Female
  • Indolizines / chemical synthesis
  • Indolizines / chemistry*
  • Indolizines / pharmacology*
  • Inhibitory Concentration 50
  • Mice
  • Myometrium / chemistry
  • Myometrium / ultrastructure
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology*
  • Rabbits
  • Rats
  • Receptors, Estrogen / agonists*
  • Receptors, Estrogen / metabolism

Substances

  • Indolizines
  • Pyrroles
  • Receptors, Estrogen
  • Estradiol
  • NNC 45-0095