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.