Tang, Kai published the artcileStructure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors, Synthetic Route of 73874-95-0, the main research area is aminopyrazine preparation cellularly active allosteric SHP2 inhibitor; Aminopyrazines; Dephosphorylase; SHP2 inhibitor.
Src homol.-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by the proto-oncogene PTPN11 is the first identified non-receptor protein tyrosine phosphatase. SHP2 dysregulation contributes to the pathogenesis of different cancers, making SHP2 a promising therapeutic target for cancer therapy. In this article, authors report the structure-guided design based on the well-characterized SHP2 inhibitor SHP099, extensive structure-activity relationship studies (SARs) of aminopyrazines, biochem. characterization and cellular potency. These medicinal chem. efforts lead to the discovery of the lead compound TK-453 I, which potently inhibits SHP2 (SHP2WT IC50 = 0.023μM, ΔTm = 7.01°C) in a reversible and noncompetitive manner. Compound I exhibits high selectivity over SHP2PTP, SHP1 and PTP1B, and may bind at the “”tunnel”” allosteric site of SHP2 as SHP099. As the key pharmacophore, the aminopyrazine scaffold not only reorganizes the cationic-π stacking interaction with R111 via the novel hydrogen bond interaction between the S atom of thioether linker and T219, but also mediates a hydrogen bond with E250. In vitro studies indicate that I inhibits proliferation of HeLa, KYSE-70 and THP-1 cells moderately and induces apoptosis of Hela cells. Further mechanistic studies suggest that I can decrease the phosphorylation levels of AKT and Erk1/2 in HeLa and KYSE-70 cells.
European Journal of Medicinal Chemistry published new progress about Arylboronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem