134603-86-4

Upstream product

• 937-12-2 4-tolyltrimethylstannane 
• 57381-39-2 2-bromo-5-fluorobenzonitrile 
• 5720-05-8 4-methylphenylboronic acid 

Downstream Products

• 1374671-63-2 4'-((5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile 
• 1374671-66-5 4'-(((5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)-4-fluoro-[1,1'-biphenyl]-2-carbonitrile 

Relevant academic research and scientific papers

Structure-based optimization of oxadiazole-based GSK-3 inhibitors

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.

Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require α-isoform specific targeting. The s

Identification of glycogen synthase kinase-3 inhibitors with a selective sting for glycogen synthase kinase-α

The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-α and GSK-3β to AD pathology and AML is ongoing. Thus, the identification of potent GSK-α-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-α inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-α selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

SUBSTITUTED QUINAZOLINONES BEARING ACIDIC FUNCTIONALGROUPS AS ANGIOTENSIN II ANTAGONISTS

Novel substituted quinazolinones of the formula (I) are useful as angiotensin II antagonists. STR1

Substituted quinazolinones as angiotensin II antagonists

Novel substituted quinazolinones of the formula (I), which are useful as angiotensin II antagonists, are disclosed. STR1