Cyclohexenyl- and dehydropiperidinyl-alkynyl pyridines as potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 20; pp. 4589 - 4593
• Main Authors: Chua, Peter C., Nagasawa, Johnny Y., Bleicher, Leo S., Munoz, Benito, Schweiger, Edwin J., Tehrani, Lida, Anderson, Jeffrey J., Cramer, Merryl, Chung, Janice, Green, Mitchell D., King, Chris D., Reyes-Manalo, Grace, Cosford, Nicholas D.P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.10.2005; Elsevier
• Subjects: Antagonist; Biological and medical sciences; CNS; Excitatory Amino Acid Antagonists - pharmacokinetics; Excitatory Amino Acid Antagonists - pharmacology; Glutamatergic system (aspartate and other excitatory aminoacids); Medical sciences; mGlu5; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Pyridines - pharmacokinetics; Pyridines - pharmacology; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - antagonists & inhibitors; CNS; mGlu5; Antagonist; Group I mglu glutamate receptor; mglu5 glutamate receptor; Sulfonamide; Intravenous administration; Acetylenic compound; Rat; Rodentia; Benzene derivatives; Selectivity; In vitro; Pyridine derivatives; In vivo; Vertebrata; Mammalia; Structure activity relation; Metabotropic receptor; Animal; Affinity; Pharmacokinetics; Chemical synthesis; Biological receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.06.099

Structure–activity relationship studies leading to the discovery of novel mGlu5 receptor antagonists are described. These compounds show high in vitro potency, have good in vivo receptor occupancy, and a reasonable intravenous pharmacokinetic profile.