Chemical & Pharmaceutical Bulletin 1995-12-01

Aromatase inhibitors: synthesis, biological activity, and structure of 1,2-imidazolylmethylcyclopentanol derivatives.

A Kato, Y Ikeda, N Sugita, T Nitta, H Enari, A Kashima, M Konno, K Niimura

文献索引：Chem. Pharm. Bull. 43(12) , 2152-8, (1995)

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摘要

Two series of 1,2-disubstituted imidazolylmethylcyclopentanol derivatives (5a-d, 10a-d) were prepared by using easily available methyl 2-oxocyclopentanecarboxylate as the starting material. Evaluation of the aromatase inhibitory activities in vitro was performed. Their activities were compared with those of a steroidal aromatase inhibitor, Formestane, and a non-steroidal inhibitor, Fadrozole. Among these compounds, the aromatase inhibitory activities of 5d, 10a, 10b, 10c, 11a, 15a, and 15b were more potent than Formestane. One compound, 1-(4-chlorobenzyl)-cis-2-(1H-imidazol-1-ylmethyl)cyclopentanol+ ++ (10a) was in particular identified as 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 configuration were determined by X-ray crystallography.