In 2011,Feng, Li; Geisselbrecht, Yann; Blanck, Sebastian; Wilbuer, Alexander; Atilla-Gokcumen, G. Ekin; Filippakopoulos, Panagis; Kraling, Katja; Celik, Mehmet Ali; Harms, Klaus; Maksimoska, Jasna; Marmorstein, Ronen; Frenking, Gernot; Knapp, Stefan; Essen, Lars-Oliver; Meggers, Eric published 《Structurally Sophisticated Octahedral Metal Complexes as Highly Selective Protein Kinase Inhibitors》.Journal of the American Chemical Society published the findings.Application of 13534-97-9 The information in the text is summarized as follows:
The generation of synthetic compounds with exclusive target specificity is an extraordinary challenge of mol. recognition and demands novel design strategies, in particular for large and homologous protein families such as protein kinases with more than 500 members. Simple organic mols. often do not reach the necessary sophistication to fulfill this task. Here, we present six carefully tailored, stable metal-containing compounds in which unique and defined mol. geometries with natural-product-like structural complexity are constructed around octahedral ruthenium(II) or iridium(III) metal centers. Each of the six reported metal compounds displays high selectivity for an individual protein kinase, namely GSK3α, PAK1, PIM1, DAPK1, MLCK, and FLT4. Although being conventional ATP-competitive inhibitors, the combination of the unusual globular shape and rigidity characteristics, of these compounds facilitates the design of highly selective protein kinase inhibitors. Unique structural features of the octahedral coordination geometry allow novel interactions with the glycine-rich loop, which contribute significantly to binding potencies and selectivities. The sensitive correlation between metal coordination sphere and inhibition properties suggests that in this design, the metal is located at a “”hot spot”” within the ATP binding pocket, not too close to the hinge region where globular space is unavailable, and at the same time not too far out toward the solvent where the octahedral coordination sphere would not have a significant impact on potency and selectivity. This study thus demonstrates that inert (stable) octahedral metal complexes are sophisticated structural scaffolds for the design of highly selective chem. probes.6-Bromopyridin-3-amine(cas: 13534-97-9Application of 13534-97-9) was used in this study.
6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. Amines characteristically form salts with acids; a hydrogen ion, H+, adds to the nitrogen. With the strong mineral acids (e.g., H2SO4, HNO3, and HCl), the reaction is vigorous. Salt formation is instantly reversed by strong bases such as NaOH. Neutral electrophiles (compounds attracted to regions of negative charge) also react with amines; alkyl halides (R′X) and analogous alkylating agents are important examples of electrophilic reagents.Application of 13534-97-9