Synthesis and in vitro receptor binding studies of fluorotamoxifen analogues.
We describe the synthesis of new fluorotamoxifen analogues with the fluorine atom positioned on the end of the aliphatic chain of tamoxifen. The binding of fluorotamoxifens to cytosol estrogen receptors of rat uteri was determined with [3H]estradiol (5 nM). The fluorotamoxifens had similar or superior binding affinities compared with tamoxifen. The IC50 value was as follows: tamoxifen, 5 x 10(-7) M; fluorotamoxifen (VII), 5 x 10(-7) M; N,N-diethylfluorotamoxifen (IV)-cis, 1 x 10(-6) M, and trans, 2 x 10(-7) M; and (cis) fluoromethyl-N,N-diethyltamoxifen (VI) 1 x 10(-7) M. Therefore, the fluorinated tamoxifens have potential use in imaging estrogen receptors by PET.
Yang
D J
DJ
Division of Diagnostic Imaging, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Wallace
S
S
Tansey
W
W
Wright
K C
KC
Kuang
L R
LR
Tilbury
R S
RS
Diego
I
I
Lim
J L
JL
Emran
A M
AM
Kim
E E
EE
D000818:Animals; D005260:Female; D005461:Fluorine; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D011960:Receptors, Estrogen; D013629:Tamoxifen; D005461:Fluorine; C037726:4-fluorotamoxifen