58230-70-9Relevant academic research and scientific papers
Lead optimization of the VU0486321 series of mGlu1PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool
Garcia-Barrantes, Pedro M.,Cho, Hyekyung P.,Metts, Adam M.,Blobaum, Anna L.,Niswender, Colleen M.,Conn, P. Jeffrey,Lindsley, Craig W.
, p. 751 - 756 (2016)
This Letter describes the further lead optimization of the VU0486321 series of mGlu1positive allosteric modulators (PAMs), driven by recent genetic data linking loss of function GRM1 to schizophrenia. Steep and caveat-laden SAR plagues the series, but ultimately potent mGlu1PAMs (EC50s ～5 nM) have resulted with good DMPK properties (low intrinsic clearance, clean CYP profile, modest Fu) and CNS penetration (Kps 0.25-0.97), along with up to >450-fold selectivity versus mGlu4and mGlu5.
Aromatic dicarboxamides
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, (2008/06/13)
N-(4-aminophenyl)-aromatic dicarboximides, e.g. those of the formula STR1 OR SALTS THEREOF ARE ANTICONVULSANTS.
