85963-50-4Relevant academic research and scientific papers
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.
Scalable preparation of stable and reusable silica supported palladium nanoparticles as catalysts for N-alkylation of amines with alcohols
Alshammari, Ahmad S.,Natte, Kishore,Kalevaru, Narayana V.,Bagabas, Abdulaziz,Jagadeesh, Rajenahally V.
, p. 141 - 149 (2020/01/06)
The development of nanoparticles-based heterogeneous catalysts continues to be of scientific and industrial interest for the advancement of sustainable chemical processes. Notably, up-scaling the production of catalysts to sustain unique structural features, activities and selectivities is highly important and remains challenging. Herein, we report the expedient synthesis of Pd-nanoparticles as amination catalysts by the reduction of simple palladium salt on commercial silica using molecular hydrogen. The resulting Pd-nanoparticles constitute stable and reusable catalysts for the synthesis of various N-alkyl amines using borrowing hydrogen technology without the use of any base or additive. By applying this Pd-based catalyst, functionalized and structurally diverse N-alkylated amines as well as some selected drug molecules were synthesized in good to excellent yields. Practical and synthetic utility of this Pd-based amination protocol has been demonstrated by upscaling catalyst preparation and amination reactions to several grams-scales as well as recycling of catalyst. Noteworthy, this Pd-catalyst preparation has been up-scaled to kilogram scale and catalysts prepared in both small (1 g) and large-scale (kg) exhibited similar structural features and activity.
Catalytic reduction of amides to amines by electrophilic phosphonium cations via FLP hydrosilylation
Augurusa, Alessandra,Mehta, Meera,Perez, Manuel,Zhu, Jiangtao,Stephan, Douglas W.
, p. 12195 - 12198 (2016/10/21)
A catalytic methodology for the conversion of amides to amines is reported. Of the 25 examples described, 14 examples involve the reduction of N-trifluoroacetamides to the corresponding trifluoroethylamines. These reductions are achieved by catalytic hydrosilylation of the amide mediated by an electrophilic phosphonium cation (EPC) catalyst.
NOVEL COMPOUNDS
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Page/Page column 41, (2011/02/18)
The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as in the description, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for preparing them.
NOVEL COMPOUNDS
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Page/Page column 91, (2011/08/22)
The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.
N-Substituted α-trifluoromethyl β-nitro amines in the synthesis of fluorine-containing 1,2-diamines, amino alcohols, and β-amino acids
Korotaev,Barkov,Kodess,Kutyashev,Slepukhin,Zapevalov
, p. 1886 - 1898 (2011/01/08)
Reactions of 2-diazo-1,1,1-trifluoro-3-nitropropane or 1-trifluoromethyl-2- nitroethenes with amines and amino alcohols afforded N-mono- and N,N-disubstituted α-trifluoromethyl β-nitro amines, which were used to obtain a number of trifluoromethyl-containing 1,2-diamines, amino alcohols, and β-amino acids.
Barbier conditions for reformatsky and alkylation reactions on trifluoromethyl aldimines
Dos Santos, Mickael,Crousse, Benoit,Bonnet-Delpon, Danièle
, p. 399 - 401 (2008/09/16)
β-Trifluoromethyl β-amino acids and α-trifluoromethyl α-alkyl amines can be easily prepared under Barbier conditions from trifluoromethyl aldimines in moderate to good yields. β-Trifluoromethyl β-amino acids were obtained in good enantioselectivity from t
