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.

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.

• Authors: A S Jørgensen, P Jacobsen, L B Christiansen, P S Bury, A Kanstrup, S M Thorpe, S Bain, L Naerum, K Wassermann
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 10 Issue 4 Pg. 399-402 (Feb 21 2000) ISSN: 0960-894X [Print] England
• PMID: 10714509 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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