Phenylethynyl-pyrrolo[1,2-a]pyrazine: A new potent and selective tool in the mGluR5 antagonists arena

Structure−Activity Relationships Comparing N-(6-Methylpyridin-yl)-Substituted Aryl Amides to 2-Methyl-6-(substituted-arylethynyl)pyridines or 2-Methyl-4-(substituted-arylethynyl)thiazoles as Novel Metabotropic Glutamate Receptor Subtype 5 Antagonists

“…In fact, most published mGluR5 structure–activity relationship studies have used this motif as the basis to their drug design and have primarily investigated structural modifications to the appended aryl rings on either side of the alkyne linker 19–23. Nevertheless, we and others,24–28 in an attempt to design nonalkynyl mGluR5 antagonists, have discovered several moderately active diarylamides (e.g., 3 and 4 in Figure 1), supporting our hypothesis that the acetylenic linker could be replaced.…”

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

“…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). 3–10 …”

Formoxazine, a New Pyrrolooxazine, and Two Amines from the Marine–Mudflat‐Derived Fungus Paecilomyces formosus

“…Pyrrolooxazine derivatives, such as compound 1 , have been reported not only as the synthetic intermediates during the development of antagonists of C–X–C chemokine receptor type 7 (CXCR7) and metabotropic glutamate receptor subtype 5 (mGluR5), but also as synthetic anti‐inflammatory and analgesic compounds . CXCR7 antagonists are useful in preventing tumor cell proliferation, tumor formation, tumor vascularization, metastasis, and inflammatory disease, and the mGluR5 antagonist has wide potential therapeutic application in a variety of central nervous system (CNS) disorders.…”

“…Based on the biological activity of the pyrrolooxazines reported previously, compound 1 warrants further study for its potential chemotherapeutic value against cancer, CNS disorders, inflammatory diseases, and pathogenic infections.…”