Publications by authors named "Kae Matsuda"
Article Synopsis
- Researchers optimized a previously discovered compound, propan-2-yl 4-({6-[5-(methanesulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate, which acts as a GPR119 agonist.
- A key modification involved replacing a linker oxygen with nitrogen and adding a trifluoromethyl group, leading to enhanced activity and better hERG inhibition profile compared to non-fluorinated versions.
- The final optimized compound showed increased insulin secretion and lowered glucose levels in diabetic models, highlighting its potential as an effective orally bioavailable therapy.
Article Synopsis
- Researchers discovered a new series of indolinylpyrimidine derivatives that act as potent GPR119 agonists, but one compound, identified as 2, also inhibited the hERG K channel, which is undesirable for drug development.
- They identified the methylsulfonyl group as a key factor in its interaction with the hERG channel and replaced it with a piperidinone ring at the indoline 5-position to reduce hERG inhibitory effects.
- Further modifications to improve drug properties included adding a hydroxy group to the piperidinone, leading to the identification of (3S)-3-hydroxy-1-{1-[6-({1-[3-(propan-2-yl)-1,2
Background & Aims: Increasing evidence highlights dietary fructose as a major driver of non-alcoholic fatty liver disease (NAFLD) pathogenesis, the majority of which is cleared on first pass through the hepatic circulation by enzymatic phosphorylation to fructose-1-phosphate via the ketohexokinase (KHK) enzyme. Without a current approved therapy, disease management emphasises lifestyle interventions, but few patients adhere to such strategies. New targeted therapies are urgently required.
View Article and Find Full Text PDFSulfonylureas (SUs) are widely used insulin secretagogues, but they have adverse effects including hypoglycemia and secondary failure. Fasiglifam/TAK-875, a selective GPR40 agonist, enhances glucose-stimulated insulin secretion and improves hyperglycemia. In the present study, we compared the in vivo glucose-lowering effects of fasiglifam with SUs.
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