Triphenylethylene Research Articles

337 The effect of tamoxifen on endometrial hyperplasia and cancer

The synthesis of a series of 35 substituted 3,4-diphenyl quinolines and isoquinolines is described. The majority of these molecules differ from all other triphenylethylene based antiestrogens by a different spatial location of the aminoalkyl side chain. The binding affinity of the most representative molecules (8, 9, 19, 20, 21, 23 and 25), including analogues 8 and 21 without the side chain, for the estrogen receptor α (ER)† was determined. The ability of these molecules to induce the progesterone receptor was also studied. Antiproliferative activity was evaluated on MCF-7 human breast cancer cells, while intrinsic cytotoxic/cytostatic properties resulting from interaction with other targets than ER were assayed on L1210 murine leukemia cells. Introduction of an aminoalkylamino side chain at carbon 2 confers strong cytotoxic properties to diphenylquinolines 9 and 10 as well as pure antiestrogenic activities. However, cytotoxicity is so high with respect to antiestrogenicity that the latter was clearly observable only in one case (9b). The structure of compound 9b was determined by X-ray crystallography. Molecular modeling of its docking within the hormone-binding domain of the receptor was subsequently undertaken. According to our results, the design of molecules with the side chain bound to the ethylene part of the triphenyl ethylene skeleton might generate compounds of potential pharmacological interest.

318 A rational approach to the design of anti-estrogens : The case of hydroxylated triphenylethylenes (TPE)

318 A rational approach to the design of anti-estrogens : The case of hydroxylated triphenylethylenes (TPE)

82. Steroid hormone binding to cytoplasmic receptors: additivity of the relative binding affinity (rba) increments calculated for individual substituents

The relative binding affinities of a series of twelve para-hydroxylated triphenylethylenes (TPEs) for the estradiol receptor (ER) of calf uterus cytosol were measured by a competition method. The results obtained under equilibrium conditions support the hypothesis of the additivity of the energies corresponding to each of the hydrogen-bond type interactions of di- or tri-hydroxylated TPEs with the estradiol binding site of ER and strongly suggest that, whichever ring is hydroxylated, the orientation of the TPE in the steroid binding site is always the same. A hydroxyl group in a given position always interacts with the same location within the site.Mono-hydroxylation of the highly hydrophobic non-substituted TPE skeleton led to a large increase in relative binding affinity for ER which could be explained by a dual mechanism whereby the interaction specific to the hydroxyl is accompanied by a temperature- or time-dependent binding process that is not related to the hydroxylation position.

Epoxidation of ethylenic linkages by chromic acid. II. Oxidation of triphenyl(tolyl)ethylene by chromic oxide

Abstract1,1,2‐Triphenyl‐2‐tolylethylene is oxidised by chromic oxide in acetic anhydride medium to give 1,2‐epoxy‐1,1,2‐triphenyl‐2‐tolylethane with fission products. A tentative explanation of the stability of such epoxides is given. Aqueous chromic acid oxidation brings about oxidative fission of the double bond. The ultra‐violet absorption spectrum of triphenyl(tolyl)ethylene is determined.

Epoxidation of ethylenic linkages by chromic acid. II. Oxidation of triphenyl(tolyl)ethylene by chromic oxide

Epoxidation of ethylenic linkages by chromic acid. II. Oxidation of triphenyl(tolyl)ethylene by chromic oxide

The influence of substituents on the additive reactivity of ethylene derivatives

The thermal addition of bromine to cyclohexene and phenyl ethylenes has been studied in acetic acid-carbon tetrachloride mixtures and the order of reactivity is found to be cyclohexene > styrene > triphenyl ethylene > stilbene. Polarising force of the substituent can explain to a certain extent, the difference in the reactivity between the cis and the trans-compounds.

Use of synthetic estrogenic substance chlorotrianisene (TACE) in treatment of acne.

IN AUGUST, 1952, an editorial in The Journal of the American Medical Association was devoted to a new long-acting estrogen, TACE. Because of its importance, major portions of the editorial are quoted herewith. The discovery that the synthetic compound diethylstilbestrol possessed high estrogenic activity when administered orally prompted a search for related compounds with a more prolonged activity. In 1942, Robson and his associates reported that the triphenyl ethylene derivative diethoxy-triphenyl bromoethylene ( αα -di[-p-ethoxyphenyl] β -phenyl bromoethylene), or D. B. E., showed a markedly prolonged estrogenic action in mice subjected to ovariectomy when given in doses somewhat greater than those producing a threshold response. The English investigators showed this prolonged effect was due to the fact that, on introduction into the body, D. B. E. in contrast to the estrogenic substances then available was not immediately destroyed or excreted in the urine but was stored in a number of

Reactions of Ethylenes with 1,2-Diketones in Sunlight

WE have found that ethylenes, for example, styrene, stilbene and triphenyl ethylene, react with 1,2-diketones when dissolved in benzene (thiophene-free) and exposed to sunlight. The experiments were carried out in 'Monax' glass tubes in an atmosphere of carbon dioxide. The reaction between phenanthraquinone and stilbene, which proceeds very rapidly, may be illustrated by the following scheme:

The production of vaginal mucification with the synthetic œstrogen, triphenyl ethylene

The production of vaginal mucification with the synthetic œstrogen, triphenyl ethylene

Triphenyl Ethylene

Triphenyl Ethylene

Production of Mammary Carcinomas in Mice of a Susceptible Strain by the Synthetic Œstrogen, Triphenyl Ethylene

IT is well known that in certain inbred strains of mice, many of the females develop spontaneous mammary tumours. Few or no tumours occur in the males of these strains or in the females spayed before puberty. When, however, these males are injected with Œstrone over prolonged periods, a number develop mammary tumours.

Duration of Action of Natural and Synthetic Œstrogens

IN recent communications1,2, details have been given of the oestrogenic activity of triphenyl ethylene in the mouse, the rabbit, the bitch and the monkey.

ANTAGONISM OF THE VAGINAL ACTION OF TRIPHENYL ETHYLENE BY PROGESTERONE AND TESTOSTERONE

The vaginal cornification produced by the synthetic œstrogen, triphenyl ethylene, in spayed mice is inhibited when progesterone or testosterone propionate is simultaneously administered. Testosterone is more effective than progesterone in producing this inhibition, and the results are quantitatively similar to those obtained for the antagonism between the naturally occurring œstrogen, œstrone, and progesterone and testosterone.The expenses of this investigation have been defrayed by a grant from the Medical Research Council.

THE RÔLE OF GONADOTROPIC HORMONE IN THE MAINTENANCE OF LUTEAL FUNCTION

Pseudo‐pregnant rabbits were hypophysectomized and the luteal function was maintained for 3 days by the administration of œstrin. Gonadotropic hormone from human pregnancy urine was then injected in doses which maintain the luteal function when given to pseudopregnant animals immediately after hypophysectomy, but it failed to maintain the luteal function.As it has been previously shown that the capacity of the ovary to respond to stimulation by gonadotropic hormone rapidly decreases after removal of the pituitary, it is suggested that the failure of gonadotropic hormone to maintain the luteal function in the present experiments is due to its failure to induce œstrin secretion by the ovary, and that normally gonadotropic hormone controls the luteal function through the secretion of œstrin and not by any direct action on the corpora lutea. The relevance of these findings to the problem of the existence of one or more gonadotropic hormones is discussed.When œstrin is injected into rabbits in which ovulation has been induced after hypophysectomy, active corpora lutea develop.The synthetic œstrogenic substance triphenyl ethylene can maintain the luteal function in hypophysectomized rabbits.The expenses of this research were defrayed by a grant from the Medical Research Council.

Antagonism between progesterone and the synthetic œstrogenic substance, triphenyl ethylene

The Journal of PhysiologyVolume 92, Issue 4 p. 401-405 ArticleFree Access Antagonism between progesterone and the synthetic œstrogenic substance, triphenyl ethylene J. M. Robson, J. M. RobsonSearch for more papers by this author J. M. Robson, J. M. RobsonSearch for more papers by this author First published: 14 May 1938 https://doi.org/10.1113/jphysiol.1938.sp003611Citations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume92, Issue4May 14, 1938Pages 401-405 RelatedInformation

Induction of Oestrous Changes in the Monkey and Bitch by Triphenyl Ethylene.

SummaryThe administration of triphenyl ethylene to 2 ovariectomized monkeys and one ovariectomized bitch produced changes similar to those brought about by oestrin. The bitch mated. No toxic changes were obtained in these animals or in mice injected with large doses of triphenyl ethylene.

Œstrous Reactions, including Mating, Produced by Triphenyl Ethylene

DODDS and his co-workers have described a number of synthetic substances with œstrogenic activity.