- ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS
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The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.
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Page/Page column 142
(2020/11/30)
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- Design, synthesis and biochemical studies of new 7α-allylandrostanes as aromatase inhibitors
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Two series of derivatives of 7α-allylandrostenedione, namely its 3-deoxo and 1-ene analogs, were designed and synthesised and their biochemical activity towards aromatase evaluated. In each of these series, the C-17 carbonyl group was further replaced by the hydroxyl and acetoxyl groups. The attained data pointed out that the absence of the C-3 carbonyl group led to a slightly decrease in the inhibitory activity and the introduction of an additional double bond in C-1 revealed to be a very beneficial structural change in the studied compounds (compound 12, IC50 = 0.47 μM, Ki = 45.00 nM). Furthermore, the relevance of the C-17 carbonyl group in the D-ring as a structural feature required to achieve maximum aromatase inhibitory activity is also observed for this set of derivatives.
- Varela, Carla L.,Amaral, Cristina,Correia-Da-Silva, Georgina,Carvalho, Rui A.,Teixeira, Natércia A.,Costa, Saul C.,Roleira, Fernanda M.F.,Tavares-Da-Silva, Elisiário J.
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p. 662 - 669
(2013/07/05)
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- Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803
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A series of 3-, 7-, 15-, and 16-methyl-substituted steroid analogs were synthesized via a highly stereoselective 1,6-conjugate addition. Under the catalysis of CuBr, AlMe3 reacted with four steroid dienone precursors to afford either the corresponding α-epimer of C-3 and C-7 methyl-substituted steroids as the major products, and the ratio of α/β was up to 10/1. No β-epimer has been detected for methyl addition at C-16. However, under the same reaction conditions, enantioselective methyl addition at C-15 afforded the 15β-epimer as the major product. The preliminary SAR analysis showed that the methyl substituents at C-7α and C-15β positions lead to a dramatical increase in potency against human gastric cancer cell line MGC-803.
- Li, Chun,Qiu, Wenwei,Yang, Zhengfeng,Luo, Jian,Yang, Fan,Liu, Mingyao,Xie, Juan,Tang, Jie
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experimental part
p. 859 - 869
(2010/10/18)
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- First synthesis of separable isomeric testosterone dimers showing differential activities on prostate cancer cells
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The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7α-allyltestosterone with 75% yield. The synthesis led to separable isomeric dimers (trans and cis, 2:1). X-ray diffraction crystallography, performed on monocrystal of the minor isomer, confirms the cis geometry of the double bound between the two testosterone units. MTT assays showed that the cis dimer has the highest activity against prostate cancer cell lines. The novel cis dimer is more active than the antiandrogen cyproterone acetate indicating the possible therapeutic value of this molecule.
- Bastien, Dominic,Leblanc, Valérie,Asselin, éric,Bérubé, Gervais
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experimental part
p. 2078 - 2081
(2010/07/02)
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- Functionalization of testosterone at position 7 and synthesis of 7-(3-methoxypropyl)-4-androsten-17-ol-3-one
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An efficient transformation of the terminal alkene function of 7-allyltestosterone is reported along with the stereospecific synthesis of 7-(3-methoxypropyl)-4-androsten-17-ol-3-one.
- Bastien, Dominic,Nault, Josee,Berube, Gervais
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experimental part
p. 1884 - 1892
(2009/11/30)
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- Use of aromatase-inhibitors for prophylaxis and/or treatment of benign prostatic hyperplasia
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Aromatase-inhibitors are used in a method of prophylaxis and/or treatment by therapy of prostatic hyperplasia. Pharmaceutical preparations suitable for such a use comprise an aromatase-inhibitor. A particularly preferred aromatase-inhibitor is, for example, testolactone.
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- Michael Additions to Steroidal Enones
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Reaction of steroidal 1-en-3-ones with electron-rich arene thiols gives 1α-adducts under base catalysis, whilst with acid catalysis 1α,3-bis-adducts are formed.Interaction of thiourea with 1-en-3-one systems gives a novel bridged ring structure.Various related Michael additions are described, and parameters defined for successful reaction in steroidal enones.Oxidation of the β-arylthio ketones to the sulphoxide leads to spontaneous regeneration of the enone system.
- Campbell, Malcolm M.,Jigajinni, Veerappa B.,Wightman, Richard H.
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p. 2537 - 2546
(2007/10/02)
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- 3-Keto-7 α,β-loweralkyl-Δ 5-steroids
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7(α,β)-Loweralkyl-3-keto-Δ 5 -androstanes and 7(α,β)-loweralkyl-3-keto-Δ 5 -pregnanes having anabolic, androgenic, claudogenic, progestational and anti-progestational properties are prepared by reacting 3-keto-4,6-dienic androstanes and pregnanes with organocopper reagents such as dialkyllithium cuprate. The isomerization of these compounds to yield 7(α,β)-loweralkyl-3-keto-Δ 4 -steroids is also described.
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