A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, category: piperidines, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 147539-41-1, Name is tert-Butyl 4-(methylamino)piperidine-1-carboxylate, molecular formula is C11H22N2O2. In a Article, authors is Andreev, Stanislav£¬once mentioned of 147539-41-1
Design, synthesis and biological evaluation of 7-chloro-9h-pyrimido[4,5-b]indole-based glycogen synthase kinase-3beta inhibitors
Glycogen synthase kinase-3beta (GSK-3beta) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer?s disease. We herein report on the optimization of a novel class of GSK-3beta inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure?activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successful rigidization approach afforded 3-(3aRS,7aSR)-(1-(7-chloro-9H-pyrimido[4,5-b]indol-4-yl)octahydro-6H-pyrrolo[2,3-c]pyridin-6-yl)-propanenitrile (24), which displayed an IC50 value of 130 nM on GSK-3beta and was further characterized by its metabolic stability. Finally, we disclosed the putative binding modes of the most potent inhibitors within the ATP binding site of GSK-3beta by 1 mus molecular dynamics simulations.
I hope this article can help some friends in scientific research. I am very proud of our efforts over the past few months and hope to 147539-41-1, help many people in the next few years.category: piperidines
Reference£º
Piperidine – Wikipedia,
Piperidine | C5H17203N – PubChem