56588-58-0Relevant academic research and scientific papers
16- AND 17- DEUTERATED ESTROGEN-3-SULFAMATES AS ESTROGENIC AGENTS
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Page/Page column 15; 16, (2014/08/20)
The present invention relates to novel derivatives of estradiol, in particular to deuterated derivatives of estradiol sulfamates. The present invention also relates to compositions comprising said novel derivatives, as well as to uses of said novel derivatives and compositions comprising said derivatives.
Estrone and estradiol metabolism in vivo in human breast cysts
Raju, Uma,Sepkovic, Daniel W.,Miller, William R.,Dixon, J.Michael,Bradlow, H.Leon,Levitz, Mortimer
, p. 883 - 888 (2007/10/03)
Fibrocystic disease of the breast manifesting palpable cysts express breast cyst fluids frequently containing estrogen sulfates at concentrations far exceeding those found in sera of the patient. The study explored the potential of the breast cyst to synthesize some of these estrogen sulfates. Deuterated estrone and estradiol were synthesized and either (estradiol, 4 cases or estrone, 2 cases) was injected into a cyst. The cyst was aspirated at approximately 0, 4 and 8 h, the target being 1 ml, 50% and complete aspiration respectively. Metabolites were purified sequentially by ether extraction, enzymatic hydrolysis of estrogen conjugates, chromatography on Sephadex LH 20 and identified by gas chromatography linked to mass spectrometry. The unconjugated fraction isolated from the ether extract was subjected to the same purification and detection scheme. Among the conjugates, deuterated estrone sulfate was the major metabolite of either precursor in all studies, while estradiol sulfate was not detected in any of the 6 experiments. The sulfate fractions also yielded traces of 16α-hydroxyestrone (2 studies), 4-hydroxyestrone (4 studies) and 2-hydroxyestrone (1 study). In the unconjugated fraction, one study with deuterated estradiol, 4- hydroxyestrone was obtained. In one study with deuterated estrone, traces of 2-hydroxyestrone and 16α- hydroxyestrone were obtained. These novel data are significant because patients with fibrocystic disease are at slightly elevated risk for developing breast cancer and 16α-hydroxyestrone and 4- hydroxyestrone are reported carcinogens. (C) 2000 Elsevier Science Inc.
Biosynthesis of Estrogens. Estr-5(10)-ene-3,17-dione: Isolation, Metabolism and Mechanistic Implications
Ranjith, H.,Dharmaratne, W.,Kilgore, James L.,Roitman, Esther,Shackleton, Cedric,Caspi, Eliahu
, p. 1529 - 1536 (2007/10/02)
The 16-2H2 title compound 5b constituted a significant amount of the non-aromatic metabolites recovered from incubations of 3,17-dioxo-2H3>androst-4-en-19-al 1 with placental aromatase.For the evaluation of the role of compound 5b in the elaboration of estrogens, its transformations at pH 6.5 and 7.2 in the presence and absence of microsomal placental aromatase were investigated.In the presence of the aromatase at pH 6.5, estrogens (6.8percent), products of isomerization of the double bond (Δ5(10) -> Δ4) and products of reduction of the carbonyl groups were formed.When the incubation was carried out at pH 7.2, products similar to those obtained above were isolated but in different yields.Noticeably more estrogens (22.7percent) and less of the reduced products were formed.Additionally, at pH 7.2, 10β-hydroxy-2H2>estr-4-ene-3,17-dione 4a was obtained.In the absence of the aromatase, which was replaced with bovine albumin at both pH 6.5 and 7.2, 2H2>estr-4-ene-3,17-dione 3a and its 10β-hydroxy derivative 4a were formed in large amounts and were the only products detected.The ramifications of our observations in the context of estrogen biosynthesis are discussed.
Mass Spectrometric Studies on 17β-Estradiol-17-fatty Acid Esters: Evidence for the Formation of Anion-Dipole Intermediates
Debrauwer, Laurent,Paris, Alain,Rao, Dinesh,Fournier, Francoise,Tabet, Jean-Claude
, p. 709 - 719 (2007/10/02)
The behaviour towards low collision energy processes (eV range) of (1-) prepared under negative ion chemical ionization (NICI) ammonia conditions from 17β-estradiol-17-fatty acid esters has been investigated.From such bifunctional compounds containing two acidic sites (i.e. phenol and ester groups), two isomeric forms (i.e. phenoxide and enolate forms) characterize the (1-) ion structures, whose distribution depends on the ion preparation mode.Here NICI (ammonia) provides both phenoxide and enolate forms as the (1-) species.This behaviour contrasts with the regioselectivity observed for proton abstraction from phenol under NICI (N2O) and fast atom bombardment conditions.Production of both phenoxide and enolate forms in NICI (ammonia) is demonstrated under NICI (ND3) conditions in which DO-labelled d - H>(1-) enolate ions are produced in a similar yield to unlabelled d - D>(1-) phenoxide ions.Collisionally activated dissociation (CAD) spectra of both isomeric deprotonated molecules differ strongly by the presence of two different pairs of complementary daughter ions, suggesting that these ionic species are unconvertible.This is due to a steric hindrance effect on the long-distance proton transfer.A mechanistic investigation on the formation of fragment ion pairs produced under CAD was performed with various deuterium-labelled molecules.From these experiments, evidence is provided for molecular isomerizations into ion-dipole complexes (prior to dissociation) which are structurally dependent on the initial charge location.Direct dissociation of these intermediates competes with the occurence of exothermic proton transfer(s) yielding the formation of other isomeric intermediate forms.The orientation of these proton transfers is dictated by the relative acidities of both moieties of the complex.
