From pyrroles to pyrrolo[1,2- a]pyrazinones: A new class of mGluR1 antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 5; pp. 1342 - 1345
• Main Authors: Micheli, Fabrizio, Cavanni, Paolo, Di Fabio, Romano, Marchioro, Carla, Donati, Daniele, Faedo, Stefania, Maffeis, Micaela, Sabbatini, Fabio Maria, Tranquillini, Maria Elvira
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-03-2006; Elsevier
• Subjects: Animals; Antagonist; Biological and medical sciences; CHO Cells; Cricetinae; Excitatory amino acids; Glutamatergic system (aspartate and other excitatory aminoacids); Inhibitory Concentration 50; Medical sciences; Metabotropic; mGluR1; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Pyrazines - chemistry; Pyrazines - pharmacology; Pyrrole; Pyrroles - chemistry; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Structure-Activity Relationship; Excitatory amino acids; mGluR1; Metabotropic; Antagonist; Pyrrole; Group I mglu glutamate receptor; Angular nitrogen heterocycle; Lactam; mglu1 glutamate receptor; In vitro; Ester; mGluR1: Pyrrole; Structure activity relation; Metabotropic receptor; Bicyclic compound; Affinity; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.11.049

A new class of mGluR1 noncompetitive antagonists is reported.
Exploiting the SAR of the known pyrrole derivatives, a new class of mGluR1 antagonists was developed through a cyclization of the C-2 position on the pyrrole N-1 nitrogen. The resulting pyrrolo[1,2-
a]pyrazinones are potent and noncompetitive antagonists.