Synthesis, conformational considerations, and estrogen receptor binding of diastereoisomers and enantiomers of 1-[4-[2-(dimethylamino)ethoxy]phenyl]-1,2-diphenylbutane (dihydrotamoxifen)

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effect of estrogen and antiestrogenic triphenylethylene derivatives on progesterone and estrogen receptors levels of MCF-7 cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nonisomerizable analogues of (Z)- and (E)-4-hydroxytamoxifen. Synthesis and endocrinological properties of substituted diphenylbenzocycloheptenes

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Synthesis and estrogen receptor binding of 6,7-dihydro-8-phenyl-9-[4-[2-(dimethylamino)ethoxy]phenyl]-5H-benzocycloheptene, a nonisomerizable analogue of tamoxifen. X-ray crystallographic studies

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolism of tamoxifen by isolated rat hepatocytes. Identification of l-[4-(2-hydroxyethoxy)phenyl]-1-(4-hydroxyphenyl)-2 -phenyl-1-butene and the dependence of N-oxidation on oxygen availability

Metabolism of tamoxifen by rat hepatocytes and hydrolysis of the resulting polar metabolites corresponding to conjugates with β-glucuronidase gave a major component which was identified as 1[4-(2-hydroxyethoxy)phenyl]-1- (4-hydroxyphenyl)-2-phenyl-1-butene by comparison of mass spectral properties with those of synthetic material. This compound, which was not observed as a phase I metabolite, is believed to have been found previously in rat bile and in human faeces (metabolite F) but its structure had been incorrectly assigned. Its binding affinity for the estrogen receptor was greater than that of tamoxifen but less than that of 4-hydroxytamoxifen, and it possessed a corresponding degree of antitumour activity against the MCF-7 breast cancer cell line. By carrying out the hepatocyte incubation separately under oxygen and air, it has been shown that the N-oxidation of tamoxifen is favoured by a high concentration of oxygen during in vitro metabolism but that the rate of 4-hydroxylation is not dependent on oxygen availability. © 1987.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolism of tamoxifen by isolated rat hepatocytes. Identification of the glucuronide of 4-hydroxytamoxifen

Metabolism of 4-hydroxytamoxifen by hepatocytes isolated from rats administered with phenobarbital and examination by TLC of the components not extractable into ethyl acetate revealed 4-hydroxytamoxifen β-glucuronide; its identity was confirmed by comparison of its 1H NMR spectrum with that of synthetic material. This conjugate was also formed on metabolism of tamoxifen. It bound to cytosolic oestrogen receptors with only one thousandth the affinity of 4-hydroxytamoxifen and gave a correspondingly very weak inhibition of growth of the MCF-7 human breast cancer cell line. Therefore, in contrast to reported observations on the 3-glucuronide of oestradiol, the MCF-7 cells were unable to hydrolyse 4-hydroxytamoxifen glucuronide and on this evidence, formation of this metabolite is solely a deactivation pathway. © 1990.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Non-isomerisable antiestrogens related to tamoxifen

Three types of non-isomerisable antiestrogens analogous to tamoxifen and 4-hydroxy-tamoxifen are described. Advantages of non-isomerisability are simplified synthesis, simplified metabolism profile, and that structure-activity relationships become more meaningful. The compounds described differ from tamoxifen by having an extra ring methyl group, a fused seven-membered ring system, or the central ethylene linkage saturated. These compounds retained both binding affinity to estrogen receptors and growth inhibition of MCF-7 human breast cancer cells in vitro. © 1988.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hydroxy derivatives of tamoxifen

SCOPUS: ar.jinfo:eu-repo/semantics/publishe