100817-94-5Relevant articles and documents
Structure-based optimization of oxadiazole-based GSK-3 inhibitors
Lo Monte, Fabio,Kramer, Thomas,Gu, Jiamin,Brodrecht, Martin,Pilakowski, Johannes,Fuertes, Ana,Dominguez, Juan Manuel,Plotkin, Batya,Eldar-Finkelman, Hagit,Schmidt, Boris
, p. 26 - 40 (2013/04/23)
Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases β-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3α and β, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3α and 17 nM for GSK-3β. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3α over GSK-3β, with an IC 50 of 35 nM for GSK-3α. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety.
Studies in antiparasitic agents: Part 17 - Synthesis of 2-acylamino-6-substituted-benzthiazoles as potential anthelmintic agents
Naim, S Shawkat,Singh, Sudhir K,Sharma, Satyavan
, p. 494 - 498 (2007/10/02)
The syntheses of a series of 2-acetamido-6-alkoxycarbonylbenzthiazoles (12-17), 2-alkoxycarbonylamino-6-alkoxycarbonylbenzthiazoles (18-27), 2-alkoxycarbonylamino-6-benzoylbenzthiazoles (29,30), and 2,2'-dicarbalkoxyamino-6,6'-dibenzthiazolyl oxides, sulphides and sulphones (38-43) have been carried out as structural congeners of tioxidazole (2) and related anthelmintics (3 and 4).All the benzthiazoles have been evaluated for their anthelmintic activity against Ancylostoma ceylanicum in hamsters, Hymenolepis nana in mice and Litomosoides carinii in cotton rats.Compound 15 showes more than 85percent clearance of hookworms (A. ceylanicum) at an oral dose of 250 mg/kg, while compound 24 eliminates nearly 90percent of the microfilariae in blood and also kills 50percent of the adult filarial worms at an intraperitonial dose of 30 mg/kg * 5 from the cotton rats infected with Litomosoides carinii.
