Mammalian Antifertility Agents. V. 5,6-Diarylhydronaphthalenones

Lednicer, Daniel; De, Emmert; Gw, Duncan; Sc, Lyster

doi:10.1021/jm00318a013

Cited by 10 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many compounds have been screened in the laboratory for antioestrogenic and antifertility activity (Lerner, Holthaus & Thompson 1958;Holtkamp, Greslin, Root & Lerner 1960; Harper & Walpole 1967;Lednicer, Lyster & Duncan 1967;Collins, Hobbs & Emmens 1971) but only a few have been used successfully in clinical endocrinology. Perhaps the most important compounds are clomi-0007-1188/80/130083-09 $01.00 phene (a mixture of cis and trans isomers of 1-(4-fl-diethylaminoethoxyphenyl-1 ,2-diphenyl-2-chloro-ethylene); used for the induction of ovulation (Bishop 1970) and tamoxifen (trans 1-(4-f,-dimethylaminoethoxyphenyl)l,2-diphenylbut-1-ene) used for the treatment of advanced breast cancer (Mouridsen, Palshoff, Patterson & Battersby 1978).…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Metabolic Activation of Non‐steroidal Antioestrogens: A Study of Structure‐activity Relationships

Allen¹,

Clark²,

Jordan³

1980

British J Pharmacology

View full text Add to dashboard Cite

1 The oestrogenic and antioestrogenic activities of tamoxifen and monohydroxytamoxifen have been compared with those of para-methoxy, -methyl, -fluoro, and -chloro tamoxifen in the 3 day immature rat uterine weight test. 2 The oestrogenic activity of mestranol, a steroid with low oestrogen receptor binding affinity which is believed to be demethylated to ethinyl oestradiol before exerting its effects, was less potent than ethinyl oestradiol when assayed in the 3 day immature rat uterine weight test. Similarly, paramethoxytamoxifen was less active than monohydroxytamoxifen in oestrogenic and antioestrogenic tests.3 The introduction of a para-methoxy group into tamoxifen did not affect oestrogenic or antioestrogenic activity. 4 All the derivatives of tamoxifen were partial oestrogen agonists when compared with oestradiol benzoate in the 3 d immature rat uterine weight test. All test compounds inhibited the uterotrophic activity of oestradiol benzoate (0.16 pg daily) in a dose-related manner. The order of potency was: monohydroxytamoxifen > tamoxifen _ methoxytamoxifen > p-fluoro -p-chloro _ p-methyltamoxifen. 5 Tamoxifen was approximately equiactive with its p-methyl, p-fluoro and p-chloro derivatives in the ability to inhibit [3H]-oestradiol binding to rat uterine oestrogen receptors in vitro. 6 Tamoxifen was approximately equiactive with its p-methyl and p-fluoro derivatives in the ability to inhibit vaginal cornification of ovariectomized rats upon intravaginal administration with oestradiol (3.2 ng total dose). 7 Since tamoxifen in vivo was more active as a partial oestrogen agonist and antagonist than the para substituted fluoro, chloro and methyl derivatives that cannot undergo metabolic hydroxylation to monohydroxytamoxifen, whereas the antioestrogenic activity of the compounds upon local application in the vaginal cornification test was equivalent as was their ability to inhibit [3H]-oestradiol-17# binding to the oestrogen receptor in vitro, it is suggested that at low doses; i.e. over the range of the partial agonist dose-response curve, the biological activity of tamoxifen is the net result of the activities of the parent compound and its metabolites. 8 The results demonstrate that metabolic activation of non-steroidal antioestrogens is only an advantage and not a requirement for antioestrogenic activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Evidence for the Metabolic Activation of Non‐steroidal Antioestrogens: A Study of Structure‐activity Relationships

Allen¹,

Clark²,

Jordan³

1980

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Ketones are important group in organic synthesis and nature products especially molecules containing two carbonyl groups. [15] To demonstrate the synthetic utility of this method, [a] Reaction conditions: 1 a (0.1 mmol), 2 a (1.5 mmol, 1.5 equiv), CuI (20 mol %), ligand (30 %), oxidant (1 equiv), and solvent (1.5 mL) at 115 [a] Reaction conditions: 1 (0.2 mmol), 2 a (0.3 mmol, 1.5 equiv), CuI (0.04 mmol, 2 mol %), 1.10-phen (0.06 mmol, 30 %), DTBP (0.2 mmol, 1 equiv), DCE (3.0 mL), 115 °C, 36 h, argon atmosphere, isolated yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2‐Benzyl‐3,4‐dihydronaphthalenes via Oxidative Radical Opening/Cyclization of Methylenecyclopropanes with Potassium Benzyltrifluoroborates

Nie

Chen

et al. 2022

Eur J Org Chem

View full text Add to dashboard Cite

A Copper-catalyzed benzylation of methylenecyclopropanes with potassium benzyltrifluoroborate salts has been developed to produce 2-benzyl-3,4-dihydronaphthalenes in moderate to good yields. This oxidative cyclization reaction proceeds well via a sequence of radical addition, ring-opening, and cyclization. This protocol represents a new example of methylenecyclopropane oxidative cyclization and tolerates a diverse range of substrate.

show abstract

“…The antioestrogenic and the antifertility activity shown by MER 25 confirmed the findings of other workers (Lerner, et al 1958; and provided a reference with which to compare the activities of these compounds. The established non-steroidal systemic antioestrogens MER 25,MRL 37,MRL 41,ICI 46,474,945 and U l1,100A all possess an alkylaminoethoxy side-chain, and Lednicer, Lyster & Duncan (1967), after a consideration of structureactivity relationships amongst compounds related to U-I 1, lOOA, suggested that the presence of a basic group at a given position in space is required to obtain a molecule that will antagonize the effects of concurrent oestrogen administration. Emmens, Collins, Hobbs, Miller & Owen (1969) have further suggested that the essential feature of the side-chain is its polarity rather than its basicity and that its importance lies in modifying the physical properties of the molecule.…”

Section: Resultsmentioning

confidence: 99%

Oestrogenic, Anti‐oestrogenic and Fertility Effects of Some Triphenylethanes and Triphenylethylenes Related to Ethamoxytriphetol (Mer 25)

Clark

Jordan

1976

British J Pharmacology

View full text Add to dashboard Cite

Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and anti‐oestrogenic activity in mice, and three of the compounds, α‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐α‐phenyl‐β‐4‐methoxyphenyl‐ethanol (IV), α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐bibenzyl (V) and α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐stilbene (VI), were tested for their effects on fertility in mice. Orthomethylation reduces oestrogenic and/or anti‐oestrogenic activity compared with the reported activities of non‐methylated analogues. The anti‐oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti‐oestrogens, V and VI, did not affect fertility in mice.

show abstract

Mammalian Antifertility Agents. V. 5,6-Diarylhydronaphthalenones

Cited by 10 publications

References 0 publications

Evidence for the Metabolic Activation of Non‐steroidal Antioestrogens: A Study of Structure‐activity Relationships

Evidence for the Metabolic Activation of Non‐steroidal Antioestrogens: A Study of Structure‐activity Relationships

Synthesis of 2‐Benzyl‐3,4‐dihydronaphthalenes via Oxidative Radical Opening/Cyclization of Methylenecyclopropanes with Potassium Benzyltrifluoroborates

Oestrogenic, Anti‐oestrogenic and Fertility Effects of Some Triphenylethanes and Triphenylethylenes Related to Ethamoxytriphetol (Mer 25)

Contact Info

Product

Resources

About