Nonpolar and short side chain groups at C-11beta of estradiol result in antiestrogens.

Basic Information

ID: ALA1142700

Journal: J Med Chem

Title: Nonpolar and short side chain groups at C-11beta of estradiol result in antiestrogens.

Authors: Zhang JX, Labaree DC, Hochberg RB.

Abstract: We have previously found that esters of 11beta-estradiol carboxylates are transformed from an estrogen into an antiestrogen when the 11beta-side chain is increased in length from four to five non-hydrogen atoms (n > or = 5). To understand the structural requirements for this transformation and obtain metabolically stable analogues that are not susceptible to esterase cleavage, we have synthesized other compounds having an 11beta-side chain composed of other functional groups: ketones, amides, ethers, and thiono esters. With the exception of amides, which bind poorly to the estrogen receptor (ER), all of these compounds exhibit antiestrogenic action when the side chain length is n > or = 5. Ethers (n > or = 5), studied in more detail, inhibit the action of estradiol with either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak agonists and decrease the concentration of cholesterol in blood (an hepatic estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics of selective estrogen receptor modulators.

CiteXplore: 15743187

DOI: 10.1021/jm049352x

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