- 3,17-Dioxoandrost-4-en-4-yl acetate
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The title compound, C21H28O4, has a 4-acet-oxy substituent positioned on the steroid face. The six-membered ring A assumes a conformation inter-mediate between 1,2Β-half chair and 1-sofa. A long Csp 3 - Csp 3 bond is observed in ring B and reproduced in quantum-mechanical ab initio calculations of the isolated mol-ecule using a mol-ecular-orbital Hartree-Fock method. Cohesion of the crystal can be attributed to van der Waals inter-actions and weak C - H...O hydrogen bonds. International Union of Crystallography 2007.
- Andrade,Paixao,De Almeida,Fernandes Roleira,Tavares Da Silva
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- New structure-activity relationships of A-and D-ring modified steroidal aromatase inhibitors: Design, synthesis, and biochemical evaluation
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A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3β stereochemistry (1, IC50 = 0.18 μM). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 μM) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 μM) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.
- Varela, Carla,Tavares Da Silva, Elisiário J.,Amaral, Cristina,Correia Da Silva, Georgina,Baptista, Teresa,Alcaro, Stefano,Costa, Giosuè,Carvalho, Rui A.,Teixeira, Natércia A. A.,Roleira, Fernanda M. F.
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experimental part
p. 3992 - 4002
(2012/07/30)
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- Topical treatment for mastalgia
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A composition for medicinal treatment by means of topical administration is described, which contains an aromatase inhibitor, in addition to conventional constituents of topical forms of administration. The active ingredient or the composition containing this active ingredient is especially suitable for the prophylaxis and for the treatment of mastalgia.
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- Aromatase Inhibitors. Synthesis and Biological Activity of Androstenedione Derivatives
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The synthesis and biological evaluation of androstenedione derivatives as inhibitors of estrogen biosynthesis are described.The results show that 4-hydroxy analogues are among the most potent in vitro inhibitors of the series.Esterification of the 4-hydroxy steroids generally reduced activity.Further conjugation of the 3-keto 4-ene system to give 4-hydroxy-4,6-androstadiene-3,17-dione caused more rapid inactivation of aromatase in rat ovarian microsomes than 4-hydroxyandrostenedione.Some compounds exhibited differences in activity when tested for inhibition of human placental microsomes vs. rat ovarian microsomes.The 4-hydroxyandrostenedione derivatives and their nonbulky esters were generally more potent in vitro and in vivo inhibitors than other substituted steroids in the series.Several of the synthesized compounds markedly reduce (50-81percent) estrogen levels in rats on proestrus and/or had antifertility action.To date, none of the compounds surpassed the in vivo inhibitory action of 4-hydroxy-4-androstene-3,17-dione or its 4-acetate derivative.
- Marsh, David A.,Brodie, Harry J.,Garrett, Wesley,Tsai-Morris, Chon-Hwa,Brodie, Angela M. H.
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p. 788 - 795
(2007/10/02)
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- The Synthesis of 4-Hydroxyandrost-4-ene-3,17-dione and other Potential Aromatase Inhibitors
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We describe novel syntheses of 4-hydroxyandrost-4-ene-3,17-dione (Ia) and related compounds, some containing fluorine.In addition we provide further evidence of the general tendency of 2- and 6-substituted androst-4-ene-3,17-diones to undergo rearrangement reactions, and thus provide new routes to 6-fluoro- and 2,6-difluoro-derivatives.Several of these compounds are potent aromatase inhibitors.
- Mann, John,Pietrzak, Barbara
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p. 2681 - 2685
(2007/10/02)
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