Garcia-Barrantes, Pedro M.; Cho, Hyekyung P.; Niswender, Colleen M.; Byers, Frank W.; Locuson, Charles W.; Blobaum, Anna L.; Xiang, Zixiu; Rook, Jerri M.; Conn, P. Jeffrey; Lindsley, Craig W. published the artcile< Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics>, Synthetic Route of 672948-03-7, the main research area is central nervous system metabotropic glutamate receptor antipsychotic schizophrenic.
The therapeutic potential of selective mGlu1 activation is vastly unexplored relative to the other group I mGlu receptor, mGlu5; therefore, the lab has focused considerable effort toward developing mGlu1 pos. allosteric modulators (PAMs) suitable as in vivo proof of concept tool compounds Optimization of a series of mGlu1 PAMs based on an N-(3-chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide scaffold provided I, a potent (mGlu1 EC50 = 31.8 nM) and highly CNS penetrant (brain to plasma ratio (Kp) of 1.02) mGlu1 PAM tool compound, that potentiated not only wild-type human mGlu1 but also mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenic patients. Moreover, both electrophysiol. and in vivo studies indicate the mGlu1 ago-PAMs/PAMs do not possess the same epileptiform adverse effect liability as mGlu5 ago-PAMs/PAMs and maintain temporal activity suggesting a broader therapeutic window.
Journal of Medicinal Chemistry published new progress about Antipsychotics. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Synthetic Route of 672948-03-7.
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