title: Phenyl ureas of creatinine as mGluR5 antagonists. A structure-activity relationship study of fenobam analogues.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D, S-43183 Mölndal, Sweden. andreas.wallberg@astrazeneca.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Wållberg
authors.forename: Karolina
authors.initials: K
authors.lastname: Nilsson
authors.forename: Krister
authors.initials: K
authors.lastname: Osterlund
authors.forename: Alecia
authors.initials: A
authors.lastname: Peterson
authors.forename: Susanne
authors.initials: S
authors.lastname: Elg
authors.forename: Patrick
authors.initials: P
authors.lastname: Raboisson
authors.forename: Udo
authors.initials: U
authors.lastname: Bauer
authors.forename: Lance G
authors.initials: LG
authors.lastname: Hammerland
authors.forename: Jan P
authors.initials: JP
authors.lastname: Mattsson
mesh_terms: D000577:Amides / Q000737:chemistry; D002712:Chlorides / Q000737:chemistry; D003404:Creatinine / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
chemical_list: D000577:Amides; D002712:Chlorides; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; D014508:Urea; D003404:Creatinine