Zhang, Liying published the artcileNovel Liver-targeted conjugates of Glycogen Phosphorylase Inhibitor PSN-357 for the Treatment of Diabetes: Design, Synthesis, Pharmacokinetic and Pharmacological Evaluations, Application of 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid, the main research area is diabetes glycogen phosphorylase liver conjugate PSN inhibitor pharmacokinetics.
PSN-357, an effective glycogen phosphorylase (GP) inhibitor for the treatment for type 2 diabetics, is hampered in its clin. use by the poor selectivity between the GP isoforms in liver and in skeletal muscle. In this study, by the introduction of cholic acid, 9 novel potent and liver-targeted conjugates of PSN-357 were obtained. Among these conjugates, conjugate 6 exhibited slight GP inhibitory activity (IC50 = 31.17 μM), good cellular efficacy (IC50 = 13.39 μM) and suitable stability under various conditions. The distribution and pharmacokinetic studies revealed that conjugate 6 could redistribute from plasma to liver resulting in a considerable higher exposure of PSN-357 metabolizing from 6 in liver (AUC liver/AUC plasma ratio was 18.74) vs that of PSN-357 (AUC liver/AUC plasma ratio was 10.06). In the in vivo animal study of hypoglycemia under the same dose of 50 mg/kg, conjugate 6 exhibited a small but significant hypoglycemic effects in longer-acting manners, that the hypoglycemic effects of 6 is somewhat weaker than PSN-357 from administration up to 6 h, and then became higher than PSN-357 for the rest time of the test. Those results indicate that the liver-targeted glycogen phosphorylase inhibitor may hold utility in the treatment of type 2 diabetes.
Scientific Reports published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 800401-68-7 belongs to class indole-building-block, name is 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid, and the molecular formula is C8H5ClN2O2, Application of 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles