Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor

Bioorg Med Chem. 2002 Jan;10(1):125-45. doi: 10.1016/s0968-0896(01)00257-7.

Abstract

The syntheses and in vitro pharmacological evaluation of a number of cis-3,4-diaryl-hydroxy-chromanes are reported, along with the results of a thorough in vivo profiling of the tissue-selective estrogen partial-agonist NNC 45-0781 [3, (-)-(3S,4R)-7-hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane]. These studies showed that NNC 45-0781 is a very promising candidate for the prevention of post-menopausal osteoporosis, and the treatment of other health issues related to the loss of endogenous estrogen production.

MeSH terms

  • Animals
  • Bone Density
  • Cholesterol / blood
  • Chromans / chemical synthesis*
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Drug Evaluation, Preclinical
  • Female
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Organ Size
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / agonists*
  • Vagina / cytology

Substances

  • Chromans
  • Receptors, Estrogen
  • Cholesterol
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat