69083-47-2Relevant 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.
Ru-Catalyzed Deoxygenative Transfer Hydrogenation of Amides to Amines with Formic Acid/Triethylamine
Pan, Yixiao,Luo, Zhenli,Xu, Xin,Zhao, Haoqiang,Han, Jiahong,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
supporting information, p. 3800 - 3806 (2019/07/12)
A ruthenium(II)-catalyzed deoxygenative transfer hydrogenation of amides to amines using HCO2H/NEt3 as the reducing agent is reported for the first time. The catalyst system consisting of [Ru(2-methylallyl)2(COD)], 1,1,1-tris(diphenylphosphinomethyl) ethane (triphos) and Bis(trifluoromethane sulfonimide) (HNTf2) performed well for deoxygenative reduction of various secondary and tertiary amides into the corresponding amines in high yields with excellent selectivities, and exhibits high tolerance toward functional groups including those that are reduction-sensitive. The choice of hydrogen source and acid co-catalyst is critical for catalysis. Mechanistic studies suggest that the reductive amination of the in situ generated alcohol and amine via borrowing hydrogen is the dominant pathway. (Figure presented.).
Intramolecular Pd-catalyzed anomeric C(sp3)-H activation of glycosyl carboxamides
Probst, Nicolas,Grelier, Gwendal,Ghermani, NourEddine,Gandon, Vincent,Alami, Mouad,Messaoudi, Samir
supporting information, p. 5038 - 5041 (2017/11/06)
An expedient method for the synthesis of fused glycosylquinolin-2-ones and glycosylspirooxindoles through an unprecedented intramolecular Pd-catalyzed anomeric C-H activation of the sugar moiety of 2-bromophenyl glycosylcarboxamides is reported. The scope of the reaction is broad and tolerates a wide range of functional groups.
