New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles.
Six azolyl substituted indoles were synthesized and tested for their activity to inhibit two P450 enzymes: P450 arom and P450 17a. It was observed that the introduction of alpha-imidazolylbenzyl chain at carbon 3 or 5 on indole nucleus led to very active molecules. Compounds 22, 23 and especially 33 demonstrate very high potential against P450 arom. Under our assay conditions of high substrate concentration the IC50 are 0.057, 0.0785 and 0.041 microM, respectively. These compounds are moderate inhibitors against P450 17alpha.
Le Borgne
M
M
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Nantes, France. Marc.Leborgne@sante.univ-nantes.fr
Marchand
P
P
Delevoye-Seiller
B
B
Robert
J M
JM
Le Baut
G
G
Hartmann
R W
RW
Palzer
M
M
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles