Synthesis of 6- or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors.
Two new series of benzonitrile derivatives on position 6 or 4 of indole ring were successfully synthesized via a Leimgruber-Batcho reaction. All the compounds were evaluated in vitro on the inhibition of aromatase (CYP19) and 17alpha-hydroxylase-C17,20-lyase (CYP17). The racemate, 4-[(1H-imidazol-1-yl)(1H-indol-4-yl)methyl]benzonitrile 9, showed high level of inhibitory activity towards CYP19 (IC(50)=11.5 nM).
Lézé
Marie-Pierre
MP
Université de Nantes, Nantes Atlantique Universités, Département de Pharmacochimie, IICiMed UPRES EA 1155, UFR de Sciences Pharmaceutiques, 1 rue Gaston Veil, Nantes, F-44035 Cedex 1, France.
Palusczak
Anja
A
Hartmann
Rolf W
RW
Le Borgne
Marc
M
D001141:Aromatase / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D004958:Estradiol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D011960:Receptors, Estrogen / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D047072:Aromatase Inhibitors; D006728:Hormones; D007211:Indoles; D009570:Nitriles; D011960:Receptors, Estrogen; D004958:Estradiol; C014356:benzonitrile; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase