Phenyl ureas of creatinine as mGluR5 antagonists. A structure-activity relationship study of fenobam analogues.
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.
Wållberg
Andreas
A
Department of Medicinal Chemistry, AstraZeneca R&D, S-43183 Mölndal, Sweden. andreas.wallberg@astrazeneca.com
Nilsson
Karolina
K
Osterlund
Krister
K
Peterson
Alecia
A
Elg
Susanne
S
Raboisson
Patrick
P
Bauer
Udo
U
Hammerland
Lance G
LG
Mattsson
Jan P
JP
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*
D000577:Amides; D002712:Chlorides; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; D014508:Urea; D003404:Creatinine