AROMATASE INHIBITORS - SYNTHESIS, BIOLOGICAL-ACTIVITY, AND STRUCTURE OF 1,2-IMIDAZOLYLMETHYLCYCLOPENTANOL DERIVATIVES

Two series of 1,2-disubstituted imidazolylmethylcyclopentanol derivati ves (5a-d, 10a-d) were prepared by using easily available methyl 2-oxo cyclopentanecarboxylate as the starting material. Evaluation of the ar omatase inhibitory activities in vitro was performed. Their activities were compared with those of a steroidal aromatase inhibitor, Formesta ne, and a non-steroidal inhibitor, Fadrozole. Among these compounds, t he aromatase inhibitory activities of 5d, 10a, 10b, 10c, 11a, 15a, and 15b were more potent than Formestane. One compound, enzyl)-cis-2-(1H- imidazol-1-ylmethyl)cyclopentanol (10a) was in particular identified a s a potent aromatase inhibitor in vitro, exhibiting an IC50 value of 4 x 10(-8) M. The enantiomers of 10a were separated, and their absolute configurations were determined by X-ray crystallography.