Synthesis and evaluation of 8-amino-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives as glycogen synthase kinase-3 (GSK-3) inhibitors

Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis

“…One alternative for replacing POCl 3 as the chlorinating agent/solvent is SOCl 2 , wastes of which are HCl and SO 2 without any phosphorus . Moreover, SO 2 can be removed through our previously reported process .…”

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

“…In continuation of this study, herein we report an effective approach to the synthesis of new phosphonylated triazolopyridine derivatives by reacting chloroethynylphosphonates with 2-hydrazinylpyridines. The triazolopyridine ring is a structural fragment that is present in a number of drugs and [1,2,4]triazolo[4,3- a ]pyridines were shown to have herbicidal [5–6], antifungal [7], neuroprotective [8–9] and antibacterial activity [10]. In addition, [1,2,4]triazolopyridine has been used as electron-acceptor unit in the synthesis of organic light emitting diodes (OLED) [11].…”

Application of Fragment-Based de Novo Design to the Discovery of Selective Picomolar Inhibitors of Glycogen Synthase Kinase-3 Beta

“…A variety of GSK3β inhibitors have been developed in recent decades through intensive drug discovery programs. − Despite the achievements in both high biochemical potency and structural diversity, the small molecule-based therapeutic approaches to suppress the activity of GSK3β have often been unsuccessful due in a large part to the poor selectivity against the other kinases. − Off-target inhibition may induce serious side effects because most kinases are involved in important cellular functions. Although a number of GSK3β inhibitors have claimed to be selective in the literature, most of them were tested against a limited set of kinases − ,, whereas a high degree of selectivity over off-target kinases was required for a master regulatory kinase such as GSK3β. We therefore aim to identify GSK3β inhibitors that are highly selective against a broad panel of kinases.…”