- New estrogen receptor antagonists. 3,20-Dihydroxy-19-norpregna-1,3,5(10)-trienes: Synthesis, molecular modeling, and biological evaluation
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New estrogen receptor α (ERα) antagonists – 3,20-dihydroxy-19-norpregna-1,3,5(10)-trienes containing an additional carbocyclic ring D′ at the 16α,17α positions – were synthesized. The effects of the new compounds on the MCF-7 breast cancer cells and ERα activation were investigated. All the steroids studied were synthesized starting from estrone methyl ether. The scaffold of compounds containing the six-membered ring D′ was constructed via the Diels–Alder reaction of butadiene with 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one 5. The hydrogenation of primary 16α,17α-cyclohexeno-adduct 7 followed by 3-demethylation (by HBr–AcOH) and reduction of 20-oxo group (by LiAlH4) or in one step by DIBAH gave target mono- and dihydroxy steroids 9–11. The Corey–Chaykovsky reaction of the same 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one 5 gave 16α,17α-methylene-substituted compound. The reaction of the latter with DIBAH immediately yielded 3,20-dihydroxy-16α,17α-methyleno-19-norpregna-1,3,5(10)-triene 13. The same procedures using 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one 5 produced corresponding 3,20-dihydroxy-16,17-19-norpregna-1,3,5(10)-triene 16 and 3,20-dihydroxy-19-norpregna-1,3,5(10),16-tetraene 17. All compounds were fully characterized by 1D and 2D NMR, HRMS, and X-ray diffraction. The molecular docking showed that the target compounds can bind to ER, their binding mode being similar to that of natural estradiol. 16α,17α-Methylene- or unsubstituted compounds exhibit the highest cytotoxicity against MCF-7 cells, being simultaneously relatively weak ERα inhibitors. 3,20-Dihydroxy steroids containing the six-membered ring D′ proved to be the most effective ERα inhibitors. These compounds displayed moderate cytotoxicity comparable of that of tamoxifen and showed no toxic effect on MCF-10A normal, nontumorigenic epithelial cells. The new ER antagonists were found to be good candidates for further testing as agents for the treatment and prevention of ERα-positive breast cancers.
- Kuznetsov, Yury V.,Levina, Inna S.,Scherbakov, Alexander M.,Andreeva, Olga E.,Fedyushkina, Irina V.,Dmitrenok, Andrey S.,Shashkov, Alexander S.,Zavarzin, Igor V.
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p. 670 - 682
(2017/12/08)
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- Synthesis of novel 17-(5′-iodo)triazolyl-3-methoxyestrane epimers via Cu(I)-catalyzed azide-alkyne cycloadditon, and an evaluation of their cytotoxic activity in vitro Dedicated to Professor Irén Vincze on the occasion of her 85th birthday
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The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 3-methoxyestrane 17α- and 17β-azide epimers (3 and 5) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-f and 11a-f). If the Ph3P in the clas
- Schneider, Gyula,G?rbe, Tamás,Mernyák, Erzsébet,W?lfling, János,Holczbauer, Tamás,Czugler, Mátyás,Sohár, Pál,Minorics, Renáta,Zupkó, István
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p. 153 - 165
(2015/05/19)
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- E-Ring extended estrone derivatives: introduction of 2-phenylcyclopentenone to the estrone D-ring via an intermolecular Pauson-Khand reaction
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An expedient synthetic route to E-ring extended estrone derivatives is reported. Estrone-derived cyclopentenones were accessed by an intermolecular Pauson-Khand (PK) cycloaddition. It was found that electron donating and withdrawing substituents in the arylalkyne increased and decreased the yields of PK products, respectively. The stereochemistry of the products was elucidated by X-ray and NMR studies.
- Kaasalainen, Emmi,Tois, Jan,Russo, Luca,Rissanen, Kari,Helaja, Juho
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p. 5669 - 5672
(2007/10/03)
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- Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods
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The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human semiochemical, e.g. an Androstane steroid, or a pharmaceutical composition containing a semiochemical, such that the ligand semiochemical binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids.
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- 17-Methyleneandrostan-3alpha-ol analogs as CRH inhibitors
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17-Methyleneandrostan-3α-ol analogs are useful as corticotropin releasing hormone (CRH) inhibitors, and especially as anti-depressants, when administered to the vomeronasal organ. An improved synthesis of 17-methylenandrost-4-en-3α-ol is disclosed.
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- Facile synthesis of 17-formyl steroids via palladium-catalyzed homogeneous carbonylation reaction.
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17-formyl-androst-16-ene and its analogues were synthesized from the corresponding 17-iodo-16-ene derivatives in palladium-catalyzed formylation reaction using tributyltin hydride as hydrogen source under mild reaction conditions. The formation of androst-16-ene and its isomerization products, as well as that of analogous steroidal olefins as side-products, was found to be dependent on the reaction conditions. The formylation reaction tolerates various functional groups on the A and B rings of the steroids. Copyright 2002 Elsevier Science Inc.
- Petz, Andrea,Horvath, Judit,Tuba, Zoltan,Pinter, Zoltan,Kollar, Laszlo
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p. 777 - 781
(2007/10/03)
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- 19-nor-cholane steroids as neurochemical initators of change in human hypothalamic function
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The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human vomeropherin, e.g. a 19-nor cholane steroid, or a pharmaceutical composition containing a vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids.
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- Steroids as neurochemical stimulators of the VNO to alleviate pain
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The invention relates to a method of alleviating pain. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers.
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- Steroids as neurochemical stimulators of the VNO to alleviate symptoms of PMS and anxiety
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The invention relates to a method of alleviating the symptoms of PMS and anxiety. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers.
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- Steroids as neurochemical stimulators of the VNO to treat paroxistic tachycardia
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The invention relates to a method of alleviating the symptoms of PMS and anxiety. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers.
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- Chloromethanesulfonate as an efficient leaving group: Rearrangement of the carbon-carbon bond and conversion of alcohols into azides and nitriles
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The chloromethanesulfonate (monochlate) served as an efficient leaving group for rearrangement of the carbon-carbon bond and conversion of alcohols into azides and nitriles. The treatment of the monochlate 16a with zinc acetate in dioxane at 90 °C effected migration of the 4α-methyl group to give alkene 17a. Upon similar treatment of the monochlates 22a, 25a, 28a, and 31a with zinc acetate, the carbon-carbon bonds antiperiplanar to the hydroxyl groups efficiently migrated to afford the alkenes 23a, 26a-c, 29a,b, and 32a, respectively. In the case of the diol 40, the monochlate was converted into the ketone 41 via a rearrangement-ring expansion. The reaction of the monochlates 44a, 47a, 49a, 52a, and 57a with sodium azide or lithium azide in N,N-dimethylformamide efficiently afforded the azides with inversion of the configuration. The introduction of a nitrile group to the sterically hindered alcohol 59 was performed in high yield by the reaction of the monochlate 60a with sodium cyanide.
- Shimizu, Takeshi,Ohzeki, Tomoya,Hiramoto, Katsuya,Hori, Nobuyuki,Nakata, Tadashi
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p. 1373 - 1385
(2007/10/03)
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- 19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function
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The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human vomeropherin, e.g. a 19-nor cholane steroid, or a pharmaceutical composition containing a vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids.
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- Reductive cleavage of N,N,N',N'-tetramethylphosphorodiamidate with lithium naphthalenide. A convenient procedure for deoxygenation of alcohols
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A simple, effective alternative procedure has been developed for the reductive cleavage of the N,N,N,'N'-tetramethylphosphorodiamidate group, using lithium naphthalenide as the reagent.
- Liu, Hsing-Jang,Shang, Xiao
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p. 367 - 370
(2007/10/03)
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- Syntheses of Δ16-17(Trialkylstannyl)steroids from 17-Ketosteroids. II
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The oxidation of the hydrazones of 17-ketosteroids by iodine yields Δ16-17-iodosteroids (2, 4).Starting with 2 or 8 (the 3-tetrahydropyranylether of 4) and lithium(tributyl)stannate, Δ16-17(tributylstannyl)steroids (5, 9) are synthesized.The reaction is catalyzed by electronrich complexes of nickel and palladium.In the course of side reactions Δ16-olefines (6, 10) and the "dimers" 7 and 11, the products of a cross coupling of the Δ16-17-iodosteroids, and the Δ16-17-tributylstannylsteroids are obtained.The mechanisms of these side-reaction and the influence of the solvent (THF, HMPA) are discussed.The tributylstannylsteroids are to be used as intermediates for the syntheses of steroid hormones from the 17-ketosteroids.
- Schweder, Bernd,Uhlig, Egon
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p. 223 - 228
(2007/10/02)
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- CYCLIC HYDROCARBONS WITH AN AMINOALKYL SIDECHAIN
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Provided are cyclic hydrocarbons of Formula I with an aminoalkyl sidechain that are useful for treating phospholipase A2 mediated conditions, diabetes, and obesity.
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- PALLADIUM-CATALYZED REDUCTION OF ENOL TRIFLATES TO ALKENES
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Enol triflates react with trialkylammonium formate-palladium reagent to give alkenes.
- Cacchi, Sandro,Morera, Enrico,Ortar, Giorgio
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p. 4821 - 4824
(2007/10/02)
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- Alkali Metal O,O-Diethyl Phosphorotelluroates, a Reagent Class for Deoxygenation of Epoxides, Especially Terminal Epoxides
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Epoxides are deoxygenated to olefins by alkali metal O,O-diethyl phosphorotelluroates.These reagents can be used in stoichiometric quantities or they can be generated continuously in situ from tellurium under conditions that approach a catalytic nature with respect to the metal.Terminal epoxides are deoxygenated most readily, but the reaction does work for other types.In the case of epoxides formally derived from acyclic olefins, the Z compound reacts more easily than the E isomer and the deoxygenation is stereospecific. 1,2-Epoxycyclohexanes react faster than 1,2-epoxycyclopentanes.Selective deoxygenations, especially those in favor of terminal epoxides, are possible.
- Clive, Derrick L. J.,Menchen, Steven M.
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p. 2347 - 2354
(2007/10/02)
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