519156-25-3Relevant academic research and scientific papers
One-Pot, Modular Approach to Functionalized Ketones via Nucleophilic Addition of Alkyllithium Reagents to Benzamides and Pd-Catalyzed α-Arylation
Wolters, Alexander T.,Hornillos, Valentin,Heijnen, Dorus,Giannerini, Massimo,Feringa, Ben L.
, p. 2622 - 2625 (2016/04/26)
An efficient, in situ sequential 1,2-addition of alkyllithium reagents to benzamides followed by α-arylation of the resulting alkyl ketones is reported. The use of Pd[P(t-Bu)3]2, as catalyst for the α-arylation reaction, allows access to a wide variety of functionalized benzyl ketones in a modular way. The decomposition of the tetrahedral intermediate originated from the 1,2-addition liberates in situ a lithium amide, therefore avoiding the need of an external base for the α-arylation. The method affords good overall yields with a variety of alkyl lithium reagents, benzamides, and aryl bromides, bearing a range of functional groups with complete selectivity toward the monoarylated products.
Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta
Waibel, Michael,De Angelis, Meri,Stossi, Fabio,Kieser, Karen J.,Carlson, Kathryn E.,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.
experimental part, p. 3412 - 3424 (2009/10/23)
A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.
Antiestrogenically active 1,1,2-tris(4-hydroxyphenyl)alkenes without basic side chain: Synthesis and biological activity
Lubczyk, Veronika,Bachmann, Helmut,Gust, Ronald
, p. 1484 - 1491 (2007/10/03)
C2-Alkyl substituted derivatives of the 1,1,2-tris(4-hydroxyphenyl)ethene 3a (alkyl = Me (3b), Et (3c), Prop (3d), But (3e)) were synthesized by reaction of 1,2-bis(4-methoxyphenyl)ethanone with the appropriate alkyl halide, followed by a Grignard reaction with 4-methoxyphenylmagnesium bromide, dehydration with phosphoric acid or hydrobromic acid, and ether cleavage with BBr3. The compounds were tested for estrogen receptor (ER) binding affinity in a competition experiment with radio labeled estradiol ([3H]-E2) and for gene activation on the ER-positive MCF-7-2a cell line. All compounds showed high receptor binding affinity (RBA-value: 3b (52. 1%) > 3a (45.5%) > 3c (29.6%) > 3d (4.03%) > 3e (0.95%)). The tests on hormone dependent MCF-7-2a breast cancer cells, stably transfected with the plasmid EREwtcluc, revealed that all 1,1,2-tris(4-hydroxyphenyl)ethenes antagonized the effect of 1 nM estradiol (E2). The compounds 3b (IC50 = 15 nM) and 3c (IC50 = 10 nM) were equal in their effects to 4-hydroxytamoxifen (4OHT) (IC50 = 7 nM). Agonistic effects were low. Only 3a and 3b activated the luciferase expression (relative activation at 1 μM: 3a 60%; 3b 35%). Despite their highly antagonistic potency, the 1,1,2-tris(4-hydroxyphenyl)ethenes showed only low cytotoxic properties on the hormone sensitive MCF-7 cell line.
