- Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites
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4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100 mg of 4-hydroxyandrostenedione or 200 mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3β-hydroxy-5α-androstane-4,17-dione (2) and 3α-hydroxy-5β-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3ξ,4ξ-dihydroxy-5ξ-androstan-17-one (4, 6-11) except 3α,4α-dihydroxy-5β-androstan-17-one (5). Out of the 17β-hydroxylated analogs 4-hydroxytestosterone (18), 3β,17β-dihydroxy-5α-androstan-4-one (19), 3α,17β-dihydroxy-5β-androstan-4-one (20), 5α-androstane-3β,4β,17β-triol (21), 5α-androstane-3α,4β,17β-triol (26) and 5α-androstane-3α,4α,17β-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation.
- Kohler, Maxie,Parr, Maria K.,Opfermann, Georg,Thevis, Mario,Schloerer, Nils,Marner, Franz-Josef,Schaenzer, Wilhelm
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- C-19 steroids for cosmetic uses
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The present invention relates to novel uses of C-19 steroid compounds, in particular C-19 steroids having an androsten-17-(OR 4 )-3-one structure for cosmetic and further uses, wherein R 4 is hydrogen or an unsubstituted or substituted alkyl, aryl, acyl or any group leading to hydroxyl upon biological metabolization or chemical deprotection. The present invention particularly relates to selected C-19 steroids displaying properties of high binding affinity to androgen receptor to block dihydotestosterone from binding, while at the same time providing anabolic effects, which is useful for certain applications, particularly for influencing or controlling problems of the skin and its skin-associated body structures like cellulite, wrinkles, adipose fat tissues, hair follikles or hair growth; for influencing or controlling gland function and activity such as the sebaceous gland and other glands affecting the skin and/or perspiration. The present invention also describes a composition comprising a combination of such a compound and dimethyl isosorbide.
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Paragraph 0092
(2016/05/19)
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- C-19 steroids for treating cellulite
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The present invention relates to novel uses of C-19 steroid compounds, in particular C-19 steroids having an androsten-17-(OR4)-3-one structure for prophylactic and/or therapeutic uses, wherein R4 is hydrogen or an unsubstituted or substituted alkyl, aryl, acyl or any group leading to hydroxyl upon biological metabolization or chemical deprotection. The present invention particularly relates to selected C-19 steroids displaying properties of high binding affinity to androgen receptor to block dihydotestosterone from binding, while at the same time providing anabolic effects, which is useful for certain applicationsThe therapeutic applications particularly include concepts based on influencing or controlling collagen and related therapeutic aspects, as well as concepts making use of certain disclosed effects the mentioned C-19 steroid compounds based on blocking the androgen receptor (AR) against binding of the natural androgen, dihydrotestosterone (DHT), while primarily circumventing a direct aromatase-inhibiting effect, The present invention also describes a pharmaceutical composition comprising a combination of such a compound and dimethyl isosorbide.
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Paragraph 0063-0064
(2015/12/18)
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- Use of 4,17 beta-dihydroxyandrost-4-ene-3-one for treating cancers
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The present invention relates to novel uses of 4,17β-dihydroxyandrost-4-ene-3-one (hereinafter 4-hydroxytestosterone), to a process for their preparation, to pharmaceutical compositions containing them, and to the use of said compounds for the prophylaxis and/or treatment of hormone-dependent or hormone receptor regulated cancers in mammals.
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Page/Page column 5-6
(2008/06/13)
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- Practical preparation of diosphenols by ring opening of α,β-epoxyketones catalyzed by silica gel supported acids
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The mixed acid (H2SO4-HOAc) catalyzed ring opening of α,β-epoxyketone was the most used method for the preparation of diosphenols, but it seriously suffered from poor yields and tedious workup operations. By using silica gel supported mixed acid (H2SO 4-HOAc), a variety of α,β-epoxyketones were converted into the corresponding diosphenols in unprecedented high yields within a few minutes. Georg Thieme Verlag Stuttgart.
- Zhu, Rui,Xing, Lixin,Wang, Xinyan,Cheng, Chuanjie,Liu, Bo,Hu, Yuefei
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p. 2267 - 2271
(2008/02/09)
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- Participation of the 19-Substituent in the Conversion of 19-Hydroxyandrost-4-ene-3,17-dione into the Corresponding 4,5-Diosphenol
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The synthesis of 4,19-dihydroxyandrost-4-ene-3,17-dione from 19-hydroxy-4β,5-epoxy-5β-androstane-3,17-dione and from 4β,5,19-trihydroxy-5β-androstane-3,17-dione is described.Under various reaction conditions other products are obtained as a result of participation of the 19-hydroxy group to form cyclic ethers.The formation of two of these products, 4α,5-isopropylidene-3α-hydroxy-3β,19-epoxy-5α-androstan-17-one and 4α-hydroxy-4β,19-epoxy-5α-androstane-3,17-dione, can be avoided by treatment of the aforementioned trihydroxy dione with acetic acid in the presence of HCl.
- Hrycko, Sophia,Morand, Peter
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p. 2899 - 2904
(2007/10/02)
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