Estradiol derivatives bearing sulfur-containing substituents at the 11beta or 7alpha positions: versatile reagents for the preparation of estrogen conjugates.
Estradiol derivatives bearing HS-, HSCH(2)-, HSCH(2)CH(2)-, MeS-, MeSCH(2)-, MeSCH(2)CH(2)-, or PhCH(2)SCH(2)CH(2)-groups at the 11beta position or an HS-group at the 7alpha 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 11beta 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.
Spera
Daniela
D
Dipartimento di Chimica Bioorganica e Biofarmacia, Via Bonanno 33, 56127 Pisa, Italy.
Cabrera
Gustavo
G
Fiaschi
Rita
R
Carlson
Kathryn E
KE
Katzenellenbogen
John A
JA
Napolitano
Elio
E
D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000737:chemistry; D004966:Estrogens, Conjugated (USP) / Q000138:chemical synthesis; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis*
D045166:Estradiol Congeners; D004966:Estrogens, Conjugated (USP); D013438:Sulfhydryl Compounds; D004958:Estradiol