ABSTRACT
The 21-tri-n-butylstannyl derivatives of (17 alpha,20E)-11 alpha and beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol were synthesized and characterized. These compounds, as well as the 11-unsubstituted compound were converted via electrophilic ipso radioiododestannylation to the corresponding 21[125I]iodo analogs at the no-carrier-added level in 73-90% isolated radiochemical yields. The radiochemical 4c [IV alpha ME2, (17,20E)-21[125I]iodo-11 alpha-methoxy-19-norpregna-1,3, 5(10),20-tetraene-3,17 beta-diol] was evaluated in immature female rats and the results compared to those previously reported for 4a (IVE2) and 4b (IV beta ME2) to determine the influence of 11-substitution on the ability of the compounds to function as estrogen receptor-seeking agents in vivo. The results indicated that the uptake of 11 alpha-methoxy derivative in the target organ was substantially lower, of shorter duration, with a much smaller specific receptor binding component than the other two radioligands. The distribution profile of the three 17 alpha-iodovinyl estrogens paralleled that previously reported for the corresponding 17 alpha-ethynyl estrogens and this study suggests that the in vivo pharmacological results reported for the 17 alpha-ethynyl estrogens may be used to predict the in vivo behavior of the corresponding 17 alpha-iodovinyl analogs.
