New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives

P Sonnet; P Dallemagne; J Guillon; C Enguehard; S Stiebing; J Tanguy; R Bureau; S Rault; P Auvray; S Moslemi; P Sourdaine; G E Séralini

doi:10.1016/s0968-0896(00)00024-9

New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives

Bioorg Med Chem. 2000 May;8(5):945-55. doi: 10.1016/s0968-0896(00)00024-9.

Authors

P Sonnet¹, P Dallemagne, J Guillon, C Enguehard, S Stiebing, J Tanguy, R Bureau, S Rault, P Auvray, S Moslemi, P Sourdaine, G E Séralini

Affiliation

¹ Centre d'Etudes et de Recherche sur le Médicament de Normandie, Laboratoire de Pharmacochimie, UFR des Sciences Pharmaceutiques, Caen, France.

PMID: 10882007
DOI: 10.1016/s0968-0896(00)00024-9

Abstract

We report herein the design and the synthesis of some aryl-substituted pyrrolizine and indolizine derivatives, on the basis of a hypothetical pharmacophore structure designed to fit the catalytic site of the human cytochrome P450 aromatase. The in vitro biological evaluation of these compounds allowed us to point out two new potent non-steroidal aromatase inhibitors, MR 20494 and MR 20492, with IC50 values in the range of 0.1 microM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aromatase Inhibitors*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Indolizines / chemical synthesis*
Indolizines / chemistry
Indolizines / pharmacology*
Magnetic Resonance Spectroscopy
Microsomes / drug effects
Microsomes / enzymology
Placenta / enzymology
Pyrroles / chemical synthesis*
Pyrroles / chemistry
Pyrroles / pharmacology*
Spectrophotometry, Infrared

Substances

Aromatase Inhibitors
Enzyme Inhibitors
Indolizines
Pyrroles
indolizine