Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4 was written by Fairhurst, Robin A.;Knoepfel, Thomas;Buschmann, Nicole;Leblanc, Catherine;Mah, Robert;Todorov, Milen;Nimsgern, Pierre;Ripoche, Sebastien;Niklaus, Michel;Warin, Nicolas;Luu, Van Huy;Madoerin, Mario;Wirth, Jasmin;Graus-Porta, Diana;Weiss, Andreas;Kiffe, Michael;Wartmann, Markus;Kinyamu-Akunda, Jacqueline;Sterker, Dario;Stamm, Christelle;Adler, Flavia;Buhles, Alexandra;Schadt, Heiko;Couttet, Philippe;Blank, Jutta;Galuba, Inga;Trappe, Jorg;Voshol, Johannes;Ostermann, Nils;Zou, Chao;Berghausen, Jorg;Del Rio Espinola, Alberto;Jahnke, Wolfgang;Furet, Pascal. And the article was included in Journal of Medicinal Chemistry in 2020.Category: esters-buliding-blocks The following contents are mentioned in the article:
FGF19 signaling through the FGFR4/β-klotho receptor complex has been shown to be a key driver of growth and survival in a subset of hepatocellular carcinomas, making selective FGFR4 inhibition an attractive treatment opportunity. A kinome-wide sequence alignment highlighted a poorly conserved cysteine residue within the FGFR4 ATP-binding site at position 552, two positions beyond the gate-keeper residue. Several strategies for targeting this cysteine to identify FGFR4 selective inhibitor starting points are summarized which made use of both rational and unbiased screening approaches. The optimization of a 2-formylquinoline amide hit series is described in which the aldehyde makes a hemithioacetal reversible-covalent interaction with cysteine 552. Key challenges addressed during the optimization are improving the FGFR4 potency, metabolic stability, and solubility leading ultimately to the highly selective first-in-class clin. candidate roblitinib. This study involved multiple reactions and reactants, such as Diphenyl carbonate (cas: 102-09-0Category: esters-buliding-blocks).
Diphenyl carbonate (cas: 102-09-0) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is γ-valerolactone.Category: esters-buliding-blocks
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics