In 2018,Wodtke, Robert; Hauser, Christoph; Ruiz-Gomez, Gloria; Jaeckel, Elisabeth; Bauer, David; Lohse, Martin; Wong, Alan; Pufe, Johanna; Ludwig, Friedrich-Alexander; Fischer, Steffen; Hauser, Sandra; Greif, Dieter; Pisabarro, M. Teresa; Pietzsch, Jens; Pietsch, Markus; Loeser, Reik published 《Nε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling》.Journal of Medicinal Chemistry published the findings.Recommanded Product: Methyl 5-bromopicolinate The information in the text is summarized as follows:
Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiol. and pathophysiol. conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of Nε-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomog. The determined inhibitory activities ranged from 100 to 10,000 M-1 s-1, which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the mol. recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability. The experimental part of the paper was very detailed, including the reaction process of Methyl 5-bromopicolinate(cas: 29682-15-3Recommanded Product: Methyl 5-bromopicolinate)
Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. Pyridine and its simple derivatives are stable and relatively unreactive liquids, with strong penetrating odours that are unpleasant.Recommanded Product: Methyl 5-bromopicolinate