6885-48-9Relevant articles and documents
Synthesis and biochemical characterization of a series of 17α-perfluoroalkylated estradiols as selective ligands for estrogen receptor α
Eignerová, Barbara,Sedlák, David,Dra?ínsky, Martin,Bart?něk, Petr,Kotora, Martin
, p. 6947 - 6953 (2010)
Despite intensive research efforts, the distinct biological roles of two closely related estrogen receptors, ERα and ERβ, are only partially understood. Therefore, ligands selective for either of two isotypes are useful research tools because they allow for exerting a desired subset of biological effects mediated by only one of the receptors. Here we report on the synthesis of a new class of potent and selective ligands for ERα represented by a series of 17α-substituted estradiols bearing lipophilic perfluoroalkyl chains. These 17α-perfluoroalkylated estradiols were synthesized by Ru-catalyzed cross metathesis reactions of 17α-allyl- or 17α-vinylestradiols with perfluoroalkylpropenes. Compounds were tested in both agonistic and antagonistic modes using a panel of stable steroid receptor reporter cell lines established in U2OS cells and consisting of ERα-LBD, ERβ-LBD, GR-LBD, and MR-LBD reporters. Some of the compounds are potent and selective agonists of ERα, exhibiting weak partial to no detectable agonistic activity on ERβ. Notably, 11c is the most ERα selective ligand of the prepared compounds because it activates ERα but inhibits ERβ. In addition, some compounds are pure agonists on ERα but show mixed agonistic/antagonistic profile on ERβ which is a typical pattern observed for selective estrogen receptor modulators (SERMs).
Synthesis of 17-dihydroisoxazolyl steroids of the androstane and estrone series
Litvinovskaya,Drach,Lapchinskaya,Khripach
, p. 46 - 51 (2007/10/03)
1,3-Dipolar cycloaddition of nitrile oxides to 17β-hydroxy-17α-vinyl steroids of the estrone series proceeds both regio- and stereoselectively. The stereoselectivity of the process decreases in going to steroids of the androstane series. The major epimer has S configuration of the new chiral center.
Synthesis, receptor binding, and tissue distribution of (17α,20E)- and (17α,20Z)-21-[125I]Iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d ol
Ali,Rousseau,Ghaffari,Van Lier
, p. 1946 - 1960 (2007/10/02)
The isomeric (17α,20E)- and (17α,20Z)-(iodovinyl)estradiol derivatives 3 and 6, and their no-carrier-added (nca) [125I]iodovinyl analogues, were tested for their relative target tissue retention and binding affinity for the estrogen receptor. The (iodovinyl)estradiols 3 and 6 were prepared via destannylation of the (17α,20E)- and (17α,20Z)-tributylstannyl precursors 2 and 4 with retention of configuration. Selective formation of the E or Z isomers 2 and 4 during the reaction of 17α-ethynylestradiol 1a with tri-n-butyltin hydride was controlled by the presence or absence of the catalyst, the polarity of the solvent, and the reaction temperature. The nca [125I]iodovinyl analogues [125I]-3a and [125I]-6a were obtained in good radiochemical yield and high purity by treatment of 2a and 4a with [125I]NaI in the presence of H2O2 and chloroamine-T, respectively. Of the two isomeric iodovinyl derivatives 3 and 6, the 20Z isomer 6a exhibited the highest receptor binding affinity and the [125I]-6a gave the highest in vivo receptor-mediated target tissue uptake.
Selective Cathodic Birch Reductions
Kariv-Miller, Essie,Swenson, Karl E.,Lehman, Gaye K.,Andruzzi, Romano
, p. 556 - 560 (2007/10/02)
The electroreduction of some difficult to reduce substrates was investigated by using aqueous tetrahydrofuran, tetrabutylammonium (TBA+) electrolyte, and mercury cathodes.The reduction products formed in high yields and the current efficiencies were good.Benzene, anisole, 1,2,3,4-tetrahydro-6-methoxynaphthalene and β-estradiol 3-methyl ether reactions were carried out with constant current at room temperature and were found to be more selective than the corresponding alkali metal-ammonia reductions.Selective reduction of the carbonyl function of estrone methyl ether was achieved while the aromatic ring remained intact.The aqueous THF medium did not affect base-sensitive molecules and a reduction product from 17-α-ethynylestradiol 3-methyl ether could be obtained without loss of the ethynyl group.Most of the compounds studied did not exhibit polarographic waves.A reduction product of TBA+ was observed by cyclic voltammetry and it is proposed that TBA "amalgam" may participate as a mediator in the reduction of the organic substrates.
