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- Title
N-(4-Biphenylmethyl)imidazoles as Potential Therapeutics for the Treatment of Prostate Cancer: Metabolic Robustness Due to Fluorine Substitution?
- Authors
Frédéric Leroux; Tilman U. Hutschenreuter; Céline Charrière; Rosario Scopelliti; Rolf W. Hartmann
- Abstract
3,3',5,5'- And 2,2',6,6'-tetrafluoro-substituted 1-[(1,1'-biphenyl]-4-yl)methyl]-1H-imidazoles were synthesized as inhibitors of 17α-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.
- Subjects
IMIDAZOLES; ENZYMES; ANDROGENS; PROSTATE cancer
- Publication
Helvetica Chimica Acta, 2003, Vol 86, Issue 7, p2671
- ISSN
0018-019X
- Publication type
Article