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].
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.
Ogawa
K
K
Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Matsushita
Y
Y
Yamawaki
I
I
Kaneda
M
M
Shibata
J
J
Toko
T
T
Asao
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C064635:TAT 59