Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: potent and selective aromatase inhibitors

Marie-Pierre Lézé; Marc Le Borgne; Patricia Pinson; Anja Palusczak; Muriel Duflos; Guillaume Le Baut; Rolf W Hartmann

doi:10.1016/j.bmcl.2005.11.099

Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: potent and selective aromatase inhibitors

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1134-7. doi: 10.1016/j.bmcl.2005.11.099. Epub 2005 Dec 27.

Authors

Marie-Pierre Lézé¹, Marc Le Borgne, Patricia Pinson, Anja Palusczak, Muriel Duflos, Guillaume Le Baut, Rolf W Hartmann

Affiliation

¹ Department of Pharmacochemistry, BioCiT UPRES EA1155, Faculty of Pharmacy, Nantes University, 1 rue Gaston Veil, F-44035 Nantes Cedex, France. mpl_leze@yahoo.fr

PMID: 16380254
DOI: 10.1016/j.bmcl.2005.11.099

Abstract

The synthesis and the aromatase (CYP19) inhibitory activity of 5-[(aryl)(imidazol-1-yl)methyl]-1H-indoles were reported. Among the tested racemate compounds, 5-[(4-chlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 8b emerged as a potent CYP19 inhibitor (IC(50)=15.3 nM). Chiral chromatography allowed isolation of the (+) enantiomer 8b2, which was about twice as active as the racemate (IC(50)=9 nM).

MeSH terms

Aromatase Inhibitors / chemical synthesis*
Aromatase Inhibitors / chemistry
Aromatase Inhibitors / pharmacology*
Imidazoles / chemistry*
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology*
Inhibitory Concentration 50
Methylation
Molecular Structure
Sensitivity and Specificity
Structure-Activity Relationship
Substrate Specificity

Substances

Aromatase Inhibitors
Imidazoles
Indoles
imidazole