1192814-45-1Relevant articles and documents
GluN2A-selective pyridopyrimidinone series of nmdar positive allosteric modulators with an improved in vivo profile
Villemure, Elisia,Volgraf, Matthew,Jiang, Yu,Wu, Guosheng,Ly, Cuong Q.,Yuen, Po-Wai,Lu, Aijun,Luo, Xifeng,Liu, Mingcui,Zhang, Shun,Lupardus, Patrick J.,Wallweber, Heidi J. A.,Liederer, Bianca M.,Deshmukh, Gauri,Plise, Emile,Tay, Suzanne,Wang, Tzu-Ming,Hanson, Jesse E.,Hackos, David H.,Scearce-Levie, Kimberly,Schwarz, Jacob B.,Sellers, Benjamin D.
, p. 84 - 89 (2016)
The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca2+ and Na+. NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. Recently, we have disclosed GNE-0723 (1), a GluN2A subunit-selective and brain-penetrant positive allosteric modulator (PAM) of NMDARs. This work highlights the discovery of a related pyridopyrimidinone core with distinct structure-activity relationships, despite the structural similarity to GNE-0723. GNE-5729 (13), a pyridopyrimidinone-based NMDAR PAM, was identified with both an improved pharmacokinetic profile and increased selectivity against AMPARs. We also include X-ray structure analysis and modeling to propose hypotheses for the activity and selectivity differences.
Synthesis of new imidazopyridine nucleoside derivatives designed as maribavir analogues
Papadakis, Georgios,Gerasi, Maria,Snoeck, Robert,Marakos, Panagiotis,Andrei, Graciela,Lougiakis, Nikolaos,Pouli, Nicole
, (2020/10/18)
The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure-activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scafflold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential.
PYRIDOPYRIMIDINONES AND THEIR USE AS NMDA RECEPTOR MODULATORS
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Page/Page column 28, (2016/10/31)
The invention relates to pyridopyrimidinone compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein X, R, R2, R3, R4, R5 and R6 are as defined herein, as well as pharmaceutical compositions comprising such compounds, useful as NMDA receptor modulators in the treatment of neurological and psychiatric conditions.