2- and 3-[(Aryl)(azolyl)methyl]indoles as Potential Non-steroidal Aromatase Inhibitors

Abstract

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 μM. 28 g was also a weak inhibitor of androstenedione synthesis.

Keywords: :

• Aromatase
• 17-α-Hydroxylase/17,20-lyase
• Azoles
• Breast cancer