New discoveries in chemical research and development in 2021. We’ll be discussing some of the latest developments in chemical about CAS: 2879-20-1, Safety of 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethanone, In a article, mentioned the application of 2879-20-1, molecular formula is C10H10O3
Protein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for type 2 diabetes. Herein, we report the evolution of a previously identified 3-phenylpropanoic acid-based PTP1B inhibitor to an orally active lead compound. A series of 3-phenylpropanoic acid-based PTP1B inhibitors were synthesized, and three of them, 3-(4-(9H-carbazol-9-yl)phenyl)-5-(3,5-di-tert-butyl-4- methoxyphenyl)-5-oxopentanoic acid (9), 3-(4-(9H-carbazol-9-yl)phenyl)-5- (4?-bromo-[1,1?-biphenyl]-4-yl)-5-oxopentanoic acid (10) and 3-(4-(9H-carbazol-9-yl)-2-fluorophenyl)-5-(4-cyclohexylphenyl)-5-oxopentanoic acid (16), showed IC50 values at sub-micromolar level. Further in vivo evaluation indicated the sodium salt of 9 not only exhibited significant insulin-sensitizing and hypoglycemia effects, but also decreased the serum levels of triglyceride and total cholesterol in high-fat-diet-induced insulin resistance model mice. Preliminary in vivo pharmacokinetic studies on the sodium salt of 9 revealed its pharmacokinetic profile after oral administration in rats. These results provide proof-of-concept for the dual effects of PTP1B inhibitors on both glucose and lipid metabolisms. A sincere form of flattery: A novel protein tyrosine phosphatase 1B (PTP1B) inhibitor with a 3-phenylpropanoic acid moiety as a phosphotyrosine (pTyr) mimetic was optimized to provide an orally active lead compound with an IC50 value of 0.40 muM against PTP1B and more notably that displayed significant in vivo activity in a murine insulin resistance model.
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