Synthesis and antiestrogenic activity of the compounds related to the metabolites of (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]- 2-(4-isopropylphenyl)-1-butenyl]phenyl monophosphate (TAT-59) [corrected]

Abstract

The metabolites of (E) [corrected]-4-[1-[4-[2-dimethylamino)ethoxy]phenyl]- 2-(4-isopropylphenyl)-1-butenyl]phenyl monophosphate, TAT-59, (1), a potent antitumor agent for hormone-dependent tumors, and derivatives of TAT-59 were synthesized to confirm its proposed structure. The structure and the Z-configuration of the metabolites (2a-8a) were confirmed by comparison with synthesized authentic compounds. All of the metabolites and the derivatives of TAT-59 were tested for a binding affinity toward estrogenic receptors in vitro and antiuterotrophic activity in vivo. Most of the metabolites possessed remarkable binding affinity toward estrogenic receptors as well as fairly good antiuterotrophic activity.