Synthesis and biological evaluation of 3-(azolylmethyl)-1H-indoles and 3-(alpha-azolylbenzyl)-1H-indoles as selective aromatase inhibitors.
This present study identifies a number of azolyl-substituted indoles as potent inhibitors of aromatase. In the sub-series of 3-(azolylmethyl)-1H-indoles, four imidazole derivatives and their triazole analogues were tested. Imidazole derivatives 11 and 14 in which the benzyl moiety was substituted by 2-chloro and 4-cyano groups, respectively, were the most active, with IC50 values ranging between 0.054 and 0.050 microM. In the other sub-series, eight 3-(alpha-azolylbenzyl)-1H-indoles were prepared and tested. Compound 30, the N-ethyl imidazole derivative, proved to be an aromatase inhibitor, showing an IC50 value of 0.052 microM. All target compounds were further evaluated against 17alpha-hydroxylase/C17,20-lyase to determine their selectivity profile.
Le Borgne
Marc
M
Université de Nantes, Nantes Atlantique Universités, Biomolécules et Cibles Thérapeutique, EA1155, U.F.R. de Sciences Pharmaceutiques, 1 rue Gaston Veil, Nantes F-44035, France. marc.le-borgne@univ-nantes.fr
Marchand
Pascal
P
Nourrisson
Marie-Renee
MR
Loquet
Denis
D
Palzer
Martina
M
Le Baut
Guillaume
G
Hartmann
Rolf W
RW
D000818:Animals; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects; D015394:Molecular Structure; D010920:Placenta / Q000201:enzymology; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013737:Testis / Q000201:enzymology
D047072:Aromatase Inhibitors; D001393:Azoles; D007211:Indoles; D013254:Steroid 17-alpha-Hydroxylase