1624-73-3Relevant academic research and scientific papers
New estrogen receptor antagonists. 3,20-Dihydroxy-19-norpregna-1,3,5(10)-trienes: Synthesis, molecular modeling, and biological evaluation
Kuznetsov, Yury V.,Levina, Inna S.,Scherbakov, Alexander M.,Andreeva, Olga E.,Fedyushkina, Irina V.,Dmitrenok, Andrey S.,Shashkov, Alexander S.,Zavarzin, Igor V.
, p. 670 - 682 (2018)
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.
Synthesis of novel estrone analogs by incorporation of thiophenols via conjugate addition to an enone side chain
Kopel, Lucas C.,Ahmed, Mahmoud S.,Halaweish, Fathi T.
, p. 1119 - 1125 (2013/10/08)
Functionalized estrogen analogs have received interest due to their unique and differing biological activity compared to their parent compounds. The synthesis of a new class of 3-methoxyestrone analogs functionalized at the C17 position possessing both alkyl and aryl substituted α,β-unsaturated ketones is described, along with their thiophenol conjugate addition products.
Structural modification of 19-norprogesterone I: 17-α-substituted-11-β-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents
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, (2008/06/13)
The present invention relates, inter alia, to compounds having the general formula: in which: R1 is a member selected from the group consisting of —OCH3, —SCH3, —N(CH3)2, —NHCH3, —NC4
17β-acyl-17α-propynyl-11β-arylsteroids and their derivatives having agonist or antagonist hormonal properties
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, (2008/06/13)
The invention is directed to a novel class of 17β-acyl-17β-propynyl steroids which exhibit potent antiprogestational activity.
19-SUBSTITUTED PROGESTERONE DERIVATIVES USEFUL AS 19-HYDROXYLASE INHIBITORS
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, (2008/06/13)
19-Substituted progesterone derivatives and related compounds which are active as 19-hydroxylase inhibitors and useful as antihypertensive agents are described herein. The compounds are prepared using appropriate synthetic pathways which will vary accordi
CYCLIC HYDROCARBONS WITH AN AMINOALKYL SIDECHAIN
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, (2008/06/13)
Provided are cyclic hydrocarbons of Formula I with an aminoalkyl sidechain that are useful for treating phospholipase A2 mediated conditions, diabetes, and obesity.
Progrestationally active steroids
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, (2008/06/13)
Novel steroids having the formula STR1 wherein R1 is selected from the group consisting of methyl, ethyl, and propyl; R2 is selected from the group consisting of H and methyl; R3 is selected from the group consisting of OXO and H(OR5); STR2 wherein R4 is selected from the group consisting of H2, H(methyl), H(Cl), H(F), and =CH2 ; or STR3 wherein R is selected from the group consisting of H, methyl, Cl, and F. Q-S is selected from the group consisting of --CH=CH-- and --CH2 CH--. Also disclosed is a method for making and therapeutically using the steroids and for making the intermediates.
Oxidative Decyanation of Secondary Nitriles to Ketones
Freerksen, Robert W.,Selikson, Sandra J.,Wroble, Randall R.,Kyler, S. Keith,Watt, David S.
, p. 4087 - 4096 (2007/10/02)
Procedures for the oxidative decyanation of secondary nitriles to ketones involve (1) iodination of N-(trialkylsilyl)ketenimines derived from secondary nitriles and subsequent hydrolysis of the α-iodo nitriles with silver oxide, (2) addition of nitrosobenzene to N-(trialkylsilyl)ketenimines, (3) conversion of secondary nitriles to α-(phenylthio) nitriles and subsequent hydrolysis with N-bromosuccinimide in aqueous acetonitrile, and (4) preparation of α-hydroperoxy nitriles by direct oxygenation of anions of secondary nitriles and subsequent reductive hydrolysis with stannous chloride followed by sodium hydroxide.The latter general procedure was applied to various secondary nitriles bearing dialkyl, aryl and alkyl, and diaryl substituents to provide ketones in good yield and was extended to the oxidative decyanation of α,β-unsaturated nitriles to furnish α,β-unsaturated ketones.
