In an article, author is Shen, Jian, once mentioned the application of 4983-28-2, Application In Synthesis of 2-Chloro-5-hydroxypyrimidine, Name is 2-Chloro-5-hydroxypyrimidine, molecular formula is C4H3ClN2O, molecular weight is 130.53, MDL number is MFCD09743796, category is pyrimidines. Now introduce a scientific discovery about this category.
Structural optimization of pyrazolo[1,5-a]pyrimidine derivatives as potent and highly selective DPP-4 inhibitors
Our previous discovery of pyrazolo [1,5-a]pyrimidin-7(4H)-one scaffold-based DPP-4 inhibitors yielded two potent compounds b2 (IC50 = 79 nM) and d1 (IC50 = 49 nM) but characterized by cytotoxicity. Herein, with scaffold hopping and fragment-based drug design strategies, highly potent and selective pyrazolo [1,5-a]pyrimidine DPP-4 inhibitors were found featured by reduced or diminished cytotoxicity. Specifically, c24 (IC50 = 2 nM) exhibits a 25 to 40-fold increase of inhibitory activity respect to those of b2 and d1, respectively, 2-fold from Alogliptin (IC50 = 4 nM), and remarkable selectivity over DPP-8 and DPP-9 (>2000 fold). Further docking studies confirmed that the pyrazolo [1,5-a]pyrimidine core interacts with the S1 pocket whereas its substituted aromatic ring interacts with the sub-S1 pocket. The interactive mode in this case resembles that of Alogliptin and Trelagliptin. Further in vivo IPGTT assays in diabetic mice demonstrated that c24 effectively reduces glucose excursion by 48% at the dose of 10 mg/ kg, suggesting that c24 is worthy of further development as a potent anti-diabetes agent. (C) 2020 Elsevier Masson SAS. All rights reserved.
If you are interested in 4983-28-2, you can contact me at any time and look forward to more communication. Application In Synthesis of 2-Chloro-5-hydroxypyrimidine.
Reference:
Pyrimidine | C4H4N2 – PubChem,
,Pyrimidine – Wikipedia