89900-92-5Relevant articles and documents
Lead discovery, chemical optimization, and biological evaluation studies of novel histone methyltransferase SET7 small-molecule inhibitors
Cao, Liyuan,Ding, Hong,Han, Jie,Hou, Zeng,Li, Yuanqing,Luo, Cheng,Min, Wenjian,Niu, Ao,Yang, Peng,Zhang, Rukang
supporting information, (2020/03/23)
The post-translational modifications of histones, including histone methylation and demethylation, control the expression switch of multiple genes. SET domain-containing lysine methyltransferase 7 (SET7) is the only methyltransferase, which can specifically monomethylate lysine-4 of histone H3 (H3K4me1) and play critical roles in various diseases, including breast cancer, hepatitis C virus (HCV), atherosclerotic vascular disease, diabetes, prostate cancer, hepatocellular carcinoma, and obesity. However, several known SET7 inhibitors exhibit weak activity or poor selectivity. Therefore, the development of novel SET7 inhibitors is highly desirable and of great clinical value. In this study, we identified 2–79 as a new hit compound by structure-based virtual screening and further AlphaLISA-based biochemical evaluation. Via chemical optimization, the synthesized compound DC21 was confirmed as a potent SET7 inhibitor with an IC50 value of 15.93 μM. The interaction between DC21 and SET7 was also validated through SPR experiment. Especially, DC21 retarded proliferation of MCF7 cells with an IC50 value of 25.84 μM in cellular level. In addition, DC21 has good selectivity for several other epigenetic targets, such as SUV39H1, G9a, NSD1, DOT1L and MOF. DC21 can serve as a lead compound to develop more potential SET7 inhibitors and as a chemical probe for SET7 biological function studies.
Palladium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of amides by carbon-nitrogen bond activation
Zhou, Tongliang,Ji, Chong-Lei,Hong, Xin,Szostak, Michal
, p. 9865 - 9871 (2019/11/11)
Palladium-catalyzed Suzuki-Miyaura cross-coupling or aryl halides is widely employed in the synthesis of many important molecules in synthetic chemistry, including pharmaceuticals, polymers and functional materials. Herein, we disclose the first palladium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of amides for the synthesis of biaryls through the selective activation of the N-C(O) bond of amides. This new method relies on the precise sequence engineering of the catalytic cycle, wherein decarbonylation occurs prior to the transmetallation step. The reaction is compatible with a wide range of boronic acids and amides, providing valuable biaryls in high yields (>60 examples). DFT studies support a mechanism involving oxidative addition, decarbonylation and transmetallation and provide insight into high N-C(O) bond activation selectivity. Most crucially, the reaction establishes the use of palladium catalysis in the biaryl Suzuki-Miyaura cross-coupling of the amide bond and should enable the design of a wide variety of cross-coupling methods in which palladium rivals the traditional biaryl synthesis from aryl halides and pseudohalides.
Integration of borylation of aryllithiums and Suzuki-Miyaura coupling using monolithic Pd catalyst
Nagaki,Hirose,Moriwaki,Mitamura,Matsukawa,Ishizuka,Yoshida
, p. 4690 - 4694 (2016/07/07)
Integration of the preparation of arylboronic esters via aryllithiums and Suzuki-Miyaura coupling using monolithic Pd catalyst without an intentionally added base was achieved. A continuous operation has been done successfully for over 21 hours.
