2- and 3-[(aryl)(azolyl)methyl]indoles as potential non-steroidal aromatase inhibitors.
The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a-h and 28a-h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC50 and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28 g) was a highly potent and selective aromatase inhibitor with IC50 value of 0.025 microM. 28 g was also a weak inhibitor of androstenedione synthesis.
Lézé
Marie-Pierre
MP
Laboratoires de Chimie Organique et de Chimie Thérapeutique, UPRES EA 1155, Faculté de Pharmacie, F-44035 Nantes, France.
Le Borgne
Marc
M
Marchand
Pascal
P
Loquet
Denis
D
Kogler
Manuela
M
Le Baut
Guillaume
G
Palusczak
Anja
A
Hartmann
Rolf W
RW
D000735:Androstenedione / Q000737:chemistry; D001141:Aromatase / Q000737:chemistry / Q000187:drug effects*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000737:chemistry
C508119:3-((4-fluorophenyl)(1H-imidazol-1-yl)methyl)-1-ethyl-2-methyl-1H-indole; D047072:Aromatase Inhibitors; D007093:Imidazoles; D007211:Indoles; D013739:Testosterone; D000735:Androstenedione; D001141:Aromatase