Structure–activity relationships for the linker in a series of pyridinyl-alkynes that are antagonists of the metabotropic glutamate receptor 5 (mGluR5)

Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype

“…3,4 Many recent efforts have produced diverse heterobicylic analogs 3 , 5,6 along with other directed efforts to replace the acetylinic linker with amides 4 7 and heterocycles 5 . 8 Other reports describe homologated variants such as 6 9 and novel heterobiaryls such as 7 . 10 In terms of structural diversity, the thiopyrimidine 8 11 and fenobam 9 12 display the greatest departure from the MPEP chemotype; however, all of these scaffolds bear structural and topological similarities to MPEP and/or employed the MPEP/MTEP scaffolds as a basis for ligand design (Figure 1).…”

Neuroimaging - Clinical Applications

“…TPMA have been described in several case reports (Amato et al, 2001;Bauer et al, 2006;Chu et al, 2001;Kramer et al, 1987;Senn et al, 2003) and small case series (Canas et al, 2010a;Chan et al, 1996;Huang et al, 2009;Milligan et al, 2009;Raghavendra et al, 2007), the largest not including more than 20 patients (Canas et al, 2010b). This scarcity of reports contrast with the practice of clinicians involved in the evaluation of patients presenting with seizures, where is not so uncommon to find MRI abnormalities induced by them.…”

Antagonists at Metabotropic Glutamate Receptor Subtype 5

“…6). 29 The linker was varied where X was CH 2 , NH, O, S, or SO. Various R substituents were added to the aromatic ring, and R′ was an alkyl or part of a bicycle that included the phenyl ring.…”