Phenyl ureas of creatinine as mGluR5 antagonists. A structure–activity relationship study of fenobam analogues

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 5; pp. 1142 - 1145
• Main Authors: Wållberg, Andreas, Nilsson, Karolina, Österlund, Krister, Peterson, Alecia, Elg, Susanne, Raboisson, Patrick, Bauer, Udo, Hammerland, Lance G., Mattsson, Jan P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-03-2006; Elsevier
• Subjects: Amides - chemistry; Anxiolytic; Biological and medical sciences; Chlorides - chemistry; Creatinine - chemistry; Creatinine - pharmacology; Fenobam; Glutamatergic system (aspartate and other excitatory aminoacids); Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Inhibitory Concentration 50; Medical sciences; Metabotropic glutamate receptor; mGluR5; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Structure-Activity Relationship; Urea - chemistry; Fenobam; mGluR5; Anxiolytic; Metabotropic glutamate receptor; Human; Five membered ring; Group I mglu glutamate receptor; mglu5 glutamate receptor; Nitrogen heterocycle; Central nervous system; Benzene derivatives; Selectivity; In vitro; Encephalon; Fenobam: Metabotropic glutamate receptor; Phenylureas; Structure activity relation; Metabotropic receptor; Chlorine Organic compounds; Affinity; Benzamide derivatives; Antagonist; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.11.092

Structure–activity relationship of the mGluR5 antagonist fenobam is reported.
Fenobam (
1) was developed by McNeil Laboratories as an anxiolytic agent with an unknown molecular target in the late 1970s. In a recent publication, it was revealed that fenobam is a non-competitive mGluR5 antagonist. Herein, we present the structure–activity relationship of fenobam and its analogues and similarities between the SAR of mGluR5 antagonism and the SAR of CNS properties originally reported by McNeil are discussed.