612-03-3Relevant articles and documents
Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
Zhao, Chenxi,Tang, Chu,Li, Changhao,Ning, Wentao,Hu, Zhiye,Xin, Lilan,Zhou, Hai-Bing,Huang, Jian
, (2021/05/10)
Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
Amide Bond Formation Catalyzed by Recyclable Copper Nanoparticles Supported on Zeolite Y under Mild Conditions
Moglie, Yanina,Buxaderas, Eduardo,Mancini, Agustina,Alonso, Francisco,Radivoy, Gabriel
, p. 1487 - 1494 (2019/02/16)
A series of catalysts based on supported copper nanoparticles have been prepared and tested in the amide bond formation from tertiary amines and acid anhydrides, in the presence of tert-butyl hydroperoxide as an oxidant. Copper nanoparticles on zeolite Y (CuNPs/ZY) was found to be the most efficient catalyst for the synthesis of amides, working in acetonitrile as solvent, under ligand- and base-free conditions in air. The products were obtained in good to excellent yields and in short reaction times. The CuNPs/ZY system also exhibited higher catalytic activity than some commercially available copper and iron sources and it was reused in ten reaction cycles without any further pre-treatment. This methodology has been successfully scaled-up to a gram scale with no detriment to the yield.
Carbonylative Coupling of Alkyl Zinc Reagents with Benzyl Bromides Catalyzed by a Nickel/NN2 Pincer Ligand Complex
Andersen, Thomas L.,Donslund, Aske S.,Neumann, Karoline T.,Skrydstrup, Troels
supporting information, p. 800 - 804 (2017/12/26)
An efficient catalytic protocol for the three-component assembly of benzyl bromides, carbon monoxide, and alkyl zinc reagents to give benzyl alkyl ketones is described, and represents the first nickel-catalyzed carbonylative coupling of two sp3-carbon fragments. The method, which relies on the application of nickel complexed with an NN2-type pincer ligand and a controlled release of CO gas from a solid precursor, works well with a range of benzylic bromides. Mechanistic studies suggest the intermediacy of carbon-centered radicals.
