Estradiol derivatives bearing sulfur-containing substituents at the 11b or 7a positions: versatile reagents for the preparation of estrogen conjugates

Abstract—Estradiol derivatives bearing HS-, HSCH2 -, HSCH2 CH2 -, MeS-, MeSCH2 -, MeSCH2 CH2 -, or PhCH2 SCH2 CH2 -groups at the 11b position or an HS-group at the 7a position have been synthesized, and their binding affinity to the estrogen receptor (ER) determined. Nearly all of these substituted estrogens retain high binding affinity, and at the 11b position, the sulfur atom has an effect on ER binding that is similar to that of a carbon atom. These thiol derivatives are promising intermediates for the preparation of a variety of estradiol conjugates. The methyl sulfides, in particular, might potentially be developed as 11 C-labeled agents for imaging ER-positive tumors by positron emission tomography. Ó 2004 Elsevier Ltd. All rights reserved.