N-(4-Biphenylmethyl)imidazoles as Potential Therapeutics for the Treatment of Prostate Cancer: Metabolic Robustness Due to Fluorine Substitution?
✍ Scribed by Frédéric Leroux; Tilman U. Hutschenreuter; Céline Charrière; Rosario Scopelliti; Rolf W. Hartmann
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- German
- Weight
- 190 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
3,3′,5,5′‐ And 2,2′,6,6′‐tetrafluoro‐substituted 1‐[(1,1′‐biphenyl]‐4‐yl)methyl]‐1__H__‐imidazoles were synthesized as inhibitors of 17__α__‐hydroxylase‐C17,20‐lyase (P450 17, CYP 17). P450 17 is the key enzyme of androgen biosynthesis. Its inhibition is a novel therapeutic approach for treatment of prostate cancer. To increase the so‐far insufficient in vivo lifetime of such compounds, the metabolically sensitive positions were blocked by F‐substitution. The meta‐ and ortho‐F‐substituted compounds were prepared by selective metallation or halogen/metal permutation reactions performed on symmetrically substituted 1,1′‐biphenyls. Compared with the halogen‐free compounds, the ortho‐F‐substituted derivatives did not match the activity, whereas the meta‐F‐substituted isomers equaled or surpassed the latter.