2639-53-4Relevant academic research and scientific papers
Collisionally-induced dissociation mass spectra of organic sulfate anions
Attygalle,Garcia-Rubio,Ta,Meinwald
, p. 498 - 506 (2001)
The collisionally-induced dissociation mass spectra of a variety of organic sulfate ester anions are described and mechanistically rationalized. A cyclic syn-elimination pathway, analogous to that of the Cope elimination, is postulated for the commonly observed formation of bisulfate anion (HSO4-, m/z 97). Deuterium labeling experiments confirm that the proton transferred to oxygen during bisulfate elimination normally originates from the C-2 position, although examination of the spectra of polyfunctional steroids reveals that the proton abstracted may originate from more distant sites as well. Adamantyl, phenyl, and vinyl sulfate anions, which do not readily lend themselves to a cyclic syn-elimination, do not give rise to an m/z 97 ion. Instead, these sulfates undergo both heterolytic and homolytic S-O bond cleavages to yield an m/z M - 80 anion, resulting from loss of neutral SO3, as well as an ion at m/z 80, corresponding to SO3-·, respectively. Sulfates that can give rise to a resonance stabilized radical by homolytic C-O bond fission, as exemplified by benzyl and linalyl sulfates, can be recognized by the formation of an m/z 96 (SO4-·) ion.
In vitro metabolism studies of desoxy-methyltestosterone (DMT) and its five analogues, and in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses
Kwok, Wai Him,Kwok, Karen Y.,Leung, David K. K.,Leung, Gary N. W.,Wong, Colton H. F.,Wong, Jenny K. Y.,Wan, Terence S. M.
, p. 994 - 1005 (2015/11/10)
The positive findings of norbolethone in 2002 and tetrahydrogestrinone in 2003 in human athlete samples confirmed that designer steroids were indeed being abused in human sports. In 2005, an addition to the family of designer steroids called 'Madol' [also known as desoxy-methyltestosterone (DMT)] was seized by government officials at the US-Canadian border. Two years later, a positive finding of DMT was reported in a mixed martial arts athlete's sample. It is not uncommon that doping agents used in human sports would likewise be abused in equine sports. Designer steroids would, therefore, pose a similar threat to the horseracing and equestrian communities. This paper describes the in vitro metabolism studies of DMT and five of its structural analogues with different substituents at the 17α position (R￡H, ethyl, vinyl, ethynyl and 2H3-methyl). In addition, the in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses will be presented. The in vitro studies revealed that the metabolic pathways of DMT and its analogues occurred predominantly in the A-ring by way of a combination of enone formation, hydroxylation and reduction. Additional biotransformation involving hydroxylation of the 17α-alkyl group was also observed for DMT and some of its analogues. The oral administration experiment revealed that DVT was extensively metabolised and the parent drug was not detected in urine. Two in vivo metabolites, derived respectively from (1) hydroxylation of the A-ring and (2) di-hydroxylation together with A-ring double-bond reduction, could be detected in urine up to a maximum of 46 h after administration. Another in vivo metabolite, derived from hydroxylation of the A-ring with additional double-bond reduction and di-hydroxylation of the 17α-vinyl group, could be detected in urine up to a maximum of 70 h post-administration. All in vivo metabolites were excreted mainly as glucuronides and were also detected in the in vitro studies.
Insights into the synthesis of steroidal A-ring olefins
Varela, Carla L.,Roleira, Fernanda M. F.,Costa, Saul C. P.,Pinto, Alexandra S. C. T.,Martins, Ana I. O. S.,Carvalho, Rui A.,Teixeira, Natercia A.,Correia-Da-Silva, Georgina,Tavares-Da-Silva, Elisiario
, p. 39 - 46 (2014/02/14)
The classical synthesis, followed by purification of the steroidal A-ring Δ1-olefin, 5α-androst-1-en-17-one (5), from the Δ1-3-keto enone, (5α,17β)-3-oxo-5-androst-1-en-17-yl acetate (1), through a strategy involving the reaction of Δ1- 3-hydroxy allylic alcohol, 3β-hydroxy-5α-androst-1-en-17β-yl acetate (2), with SOCl2, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ2-olefin 6 as a by-product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5. The same synthetic strategy was applied, using the Δ4-3-keto enone, 3-oxoandrost-4-en-17β-yl acetate (8), as starting material, to prepare the potent aromatase inhibitor Δ4-olefin, androst-4-en-17-one (15). Unexpectedly, a different aromatase inhibitor, the Δ3,5-diene, androst-3,5-dien-17-one (12), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8. The data now presented show the unequal reactivity of the two steroidal A-ring Δ1- and Δ4-3- hydroxy allylic alcohol intermediates, 3β-hydroxy-5α-androst-1-en- 17β-yl acetate (2) and 3β-hydroxyandrost-4-en-17β-yl acetate (9), towards SOCl2, and provides a new strategy for the preparation of the aromatase inhibitor 12. Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by-products. Copyright
Synthesis of novel steroidal 17α-triazolyl derivatives via Cu(I)-catalyzed azide-alkyne cycloaddition, and an evaluation of their cytotoxic activity in vitro
Frank, éva,Molnár, Judit,Zupkó, István,Kádár, Zalán,W?lfling, János
scheme or table, p. 1141 - 1148 (2011/09/15)
Regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of steroidal 17α-azides with different terminal alkynes afforded novel 1,4-disubstituted triazolyl derivatives in good yields in both the estrone and the androstane series. The antiproliferative activities of the structurally related triazoles were determined in vitro on three malignant human cell lines (HeLa, MCF7 and A431), with the microculture tetrazolium assay.
2-(N-SUBSTITUTED PIPERAZINYL) STEROID DERIVATIVES
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Page/Page column 40; 70-71, (2010/06/17)
Novel chemical agents of Formula I are described herein. More specifically, 2-(N-substituted piperazinyl) pregnane and 2-(N-substituted piperazinyl) androstane derivatives exhibiting cytotoxicity on a variety of cancer cell lines are disclosed herein. (I)
Chemical synthesis of 2β-amino-5α-androstane-3α,17β-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells
Thibeault, Dominic,Roy, Jenny,DeRoy, Patrick,Poirier, Donald
, p. 5062 - 5077 (2008/12/22)
Even though few steroids are used for the treatment of leukemia, 2β-(4-methylpiperazinyl)-5α-androstane-3α,17β-diol (1) was recently reported for its ability to inhibit the proliferation of human leukemia HL-60 cells. With an efficient procedure that we had developed for the aminolysis of hindered steroidal epoxides, we synthesized a series of 2β-amino-5α-androstane-3α,17β-diol N-derivatives structurally similar to 1. Hence, the opening of 2,3α-epoxy-5α-androstan-17β-diol with primary and secondary amines allowed the synthesis of aminosteroids with diverse length, ramification, and functionalization of the 2β-side chain. Sixty-four steroid derivatives were tested for their capacity to inhibit the proliferation of HL-60 cells; thus obtaining first structure-activity relationship results. Ten aminosteroids with long alkyl chains (7-16 carbons) or bulky groups (diphenyl or adamantyl) have shown antiproliferative activity over 78% at 10 μM and superior to that of the lead compound. The 3,3-diphenylpropylamino, 4-nonylpiperazinyl and octylamino derivatives of 5α-androstane-3α,17β-diol inhibited the HL-60 cell growth with IC50 of 3.1, 4.2 and 6.4 μM, respectively. They were also found to induce the HL-60 cell differentiation.
Synthesis of 17α-amino-5α-androst-2-ene from epiandrosterone
Merlani,Amiranashvili,Kemertelidze,Papadopulos,Yannakopulu
, p. 313 - 315 (2008/02/07)
17α-Amino-5ga-androst-2-ene was synthesized from epiandrosterone via formation of the tosylate followed by nucleophilic substitution by azide and reduction with LiAlH4. The structures of the products were proved by NMR and IR spectroscopy and mass spectrometry. 2006 Springer Science+Business Media, Inc.
Novel enol esters of steroids, compositions containing such compounds, processes for their preparation and methods of treatment therewith
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, (2008/06/13)
This invention relates to novel enol esters of steroids having an antitumor activity and to the preparation thereof. The invention is also concerned with pharmaceutical compositions containing the said compounds and methods of treatment therewith.
