TY - JOUR
T1 - Fluorinated androgens and progestins
T2 - Molecular probes for androgen and progesterone receptors with potential use in positron emission tomography
AU - Brandes, S. J.
AU - Katzenellenbogen, J. A.
PY - 1987
Y1 - 1987
N2 - In order to develop imaging agents for receptor-positive tumors of the breast and prostate, we have investigated the binding affinity of several fluorine-substituted steroids in the testosterone and nortestosterone series for the androgen receptor and the progesterone receptor. The 6α- and 11β-fluoro-, and 16α-fluoroalkyl-substituted steroids were prepared by an olefin bromofluorination reaction followed by dehydrobromination or reductive debromination. The 17α-fluoromethyl derivatives were prepared by fluoride ion attack on the 17-spiroepoxide or 17-spiro sulfate and the 17α-fluoropropynyl derivative, by reaction of a propargyl alcohol precursor with diethylaminosulfur trifluoride. Of the compounds synthesized, 17α-(3-fluoro-l-propynyl)nortestosterone was found to possess the highest binding affinity and selectivity for the progesterone receptor, and 11β-fluoronordihydrotestosterone had the greatest affinity for the androgen receptor. Both receptor systems seem to tolerate reasonably well the substitution of fluorine for hydrogen.
AB - In order to develop imaging agents for receptor-positive tumors of the breast and prostate, we have investigated the binding affinity of several fluorine-substituted steroids in the testosterone and nortestosterone series for the androgen receptor and the progesterone receptor. The 6α- and 11β-fluoro-, and 16α-fluoroalkyl-substituted steroids were prepared by an olefin bromofluorination reaction followed by dehydrobromination or reductive debromination. The 17α-fluoromethyl derivatives were prepared by fluoride ion attack on the 17-spiroepoxide or 17-spiro sulfate and the 17α-fluoropropynyl derivative, by reaction of a propargyl alcohol precursor with diethylaminosulfur trifluoride. Of the compounds synthesized, 17α-(3-fluoro-l-propynyl)nortestosterone was found to possess the highest binding affinity and selectivity for the progesterone receptor, and 11β-fluoronordihydrotestosterone had the greatest affinity for the androgen receptor. Both receptor systems seem to tolerate reasonably well the substitution of fluorine for hydrogen.
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M3 - Article
C2 - 3499564
AN - SCOPUS:0023515497
SN - 0026-895X
VL - 32
SP - 391
EP - 403
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 3
ER -