Preparation and pharmacological profile of 7-(alpha-azolylbenzyl)-1H-indoles and indolines as new aromatase inhibitors.
Aromatase (P450 arom) is a target of pharmacological interest for the treatment of breast cancer. New series of 7-(alpha-azolylbenzyl)-1H-indoles and indolines were synthesized as non-steroidal inhibitors of P450 arom. Selectivity was studied towards P450 17alpha enzyme. The most active compound, 1-ethyl-7-[(imidazol-1-yl)(4-chlorophenyl)methyl]-1H-indole 12c exhibited promising relative potency (rp) of 336 (rp of aminoglutethimide=1) and most of the described azoles were active and selective towards P450 arom.
Marchand
Pascal
P
Laboratoires de Chimie Organique et de Chimie Thérapeutique, UFR des Sciences Pharmaceutiques, 1 rue Gaston Veil, 44035 Nantes Cedex, France. pascal.marchand@sante.univ-nantes.fr
Le Borgne
Marc
M
Palzer
Martina
M
Le Baut
Guillaume
G
Hartmann
Rolf W
RW
D000818:Animals; D047072:Aromatase Inhibitors; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013737:Testis / Q000201:enzymology
D047072:Aromatase Inhibitors; D001393:Azoles; D004791:Enzyme Inhibitors; D007211:Indoles; C057812:indoline; D013254:Steroid 17-alpha-Hydroxylase