Aromatase Inhibitors : Synthesis, Biological Activity, and Structure of 1,2-Imidazolylmethylcyclopentanol Derivatives

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Two series of 1,2-disubstituted imidazolylmethylcyclopentanol derivatives (5a-d, 10a-d) were prepared by using easily available metyl 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 IC_<50> value of 4×10^<-8>M. The enantiomers of 10a were separated, and their absolute configurations were determined by X-ray crystallography.
公益社団法人日本薬学会の論文
1995-12-15