23866-72-0Relevant articles and documents
Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
Abdpour, Shahin,Jalili-Baleh, Leili,Nadri, Hamid,Forootanfar, Hamid,Bukhari, Syed Nasir Abbas,Ramazani, Ali,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Khoobi, Mehdi
, (2021/03/14)
A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8–0.71 μM) and showed remarkable BuChE inhibition activity (IC50 = 1.9–0.006 μM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 μM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 μM) and BuChE (IC50 = 0.006 μM), respectively. The ligand–protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced.neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
Design and optimization of 2,3-dihydrobenzo[b][1,4]dioxine propanoic acids as novel GPR40 agonists with improved pharmacokinetic and safety profiles
Guo, Bin,Guo, Shimeng,Huang, Jing,Li, Jingya,Li, Jia,Chen, Qian,Zhou, Xianli,Xie, Xin,Yang, Yushe
, p. 5780 - 5791 (2018/11/06)
GPR40 has become a new potential therapeutic target for the treatment of diabetes due to its role in mediating the enhancement of glucose-stimulated insulin secretion in pancreatic β cells with a low risk of hypoglycemia. As an effort to extend the chemical space and identify structurally distinct GPR40 agonists with improved liver safety, a novel series of fused-ring phenyl propanoic acid analogues were designed. Comprehensive structure-activity relationship studies around novel scaffolds were conducted and led to several analogues exhibited potent GPR40 agonistic activities and high selectivity against other fatty acid receptors. Further evaluation of pharmacokinetic (PK) profiles and in vivo efficacy identified compound 40a with excellent PK properties and significant glucose-lowering efficacy during an oral glucose tolerance test. In addition, compound 40a displayed lower hepatobiliary transporter inhibition and favorable druggability. All results indicate that compound 40a is a promising candidate for further development.
ANTI-INFECTIVE AGENTS
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Page/Page column 90-92, (2018/04/12)
The present invention relates to a novel class of chromene-2-carboxamide compounds inhibitors of general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined herein, to their use in medicine, and their use as anti-infective agents in particular, to compositions containing them, to processes for their preparation and to intermediates used in such processes.