754226-40-9Relevant articles and documents
Structure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2
Yu, Jiang,Luo, Lingling,Hu, Tong,Cui, Yating,Sun, Xiao,Gou, Wenfeng,Hou, Wenbin,Li, Yiliang,Sun, Tiemin
, (2021/10/20)
The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors have lower selectivity to PARP-1 than to PARP-2, so they will inevitably have side effects. Based on the different catalytic domains of PARP-1 and PARP-2, we developed a strategy to design and synthesize highly selective PARP-1 inhibitors. Compounds Y17, Y29, Y31 and Y49 showed excellent PARP-1 inhibition, and their IC50 values were 0.61, 0.66, 0.41 and 0.96 nM, respectively. Then, Y49 (PARP-1 IC50 = 0.96 nM, PARP-2 IC50 = 61.90 nM, selectivity PARP-2/PARP-1 = 64.5) was proved to be the most selective inhibitor of PARP-1. Compounds Y29 and Y49 showed stronger inhibitory effect on proliferation in BRCA1 mutant MX-1 cells than in other cancer cells. In the MDA-MB-436 xenotransplantation model, Y49 was well tolerated and showed remarkable single dose activity. The design strategy proposed in this paper is of far-reaching significance for the further construction of the next generation of selective PARP-1 inhibitors.
Convergent Total Synthesis of Lamellarins and Their Congeners
Morikawa, Daiki,Morii, Kazuki,Yasuda, Yuto,Mori, Atsunori,Okano, Kentaro
, p. 8603 - 8617 (2020/07/16)
A convergent total synthesis of lamellarins S and Z is described. The synthesis features a halogen dance of an easily accessible α,β-dibromopyrrole promoted by an ester moiety. The resultant β,β′-dibromopyrrole undergoes a ligand-controlled Suzuki-Miyaura coupling to provide a range of diarylated pyrrole derivatives. The established synthetic method was also applicable to the synthesis of ningalin B and lukianols A and B.
Iron-Catalyzed Borylation of Aryl Ethers via Cleavage of C-O Bonds
Zeng, Xiaoqin,Zhang, Yuxuan,Liu, Zhengli,Geng, Shasha,He, Yun,Feng, Zhang
, p. 2950 - 2955 (2020/04/15)
Herein, we report the iron-catalyzed borylation of aryl ethers and aryl amines via cleavage of C-O and C-N bonds. This protocol does not require the use of Grignard reagents and displays a broad substrate scope, which allows the late-stage borylation. It also provides facile access to multisubstituted arenes through C-H functionalization using 2-pyridyloxy as the directing group.
