title: Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: potent and selective aromatase inhibitors.
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).
authors.affiliation: Department of Pharmacochemistry, BioCiT UPRES EA1155, Faculty of Pharmacy, Nantes University, 1 rue Gaston Veil, F-44035 Nantes Cedex, France. mpl_leze@yahoo.fr
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Lézé
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
authors.forename: Patricia
authors.initials: P
authors.lastname: Pinson
authors.forename: Anja
authors.initials: A
authors.lastname: Palusczak
authors.forename: Muriel
authors.initials: M
authors.lastname: Duflos
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Baut
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008745:Methylation; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D047072:Aromatase Inhibitors; D007093:Imidazoles; D007211:Indoles; C029899:imidazole