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

Andreas Wållberg; Karolina Nilsson; Krister Osterlund; Alecia Peterson; Susanne Elg; Patrick Raboisson; Udo Bauer; Lance G Hammerland; Jan P Mattsson

doi:10.1016/j.bmcl.2005.11.092

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

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1142-5. doi: 10.1016/j.bmcl.2005.11.092. Epub 2005 Dec 27.

Authors

Andreas Wållberg¹, Karolina Nilsson, Krister Osterlund, Alecia Peterson, Susanne Elg, Patrick Raboisson, Udo Bauer, Lance G Hammerland, Jan P Mattsson

Affiliation

¹ Department of Medicinal Chemistry, AstraZeneca R&D, S-43183 Mölndal, Sweden. andreas.wallberg@astrazeneca.com

PMID: 16380255
DOI: 10.1016/j.bmcl.2005.11.092

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.

MeSH terms

Amides / chemistry
Chlorides / chemistry
Creatinine / chemistry*
Creatinine / pharmacology*
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology*
Inhibitory Concentration 50
Molecular Structure
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / metabolism
Structure-Activity Relationship
Urea / chemistry*

Substances

Amides
Chlorides
Imidazoles
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
fenobam
Urea
Creatinine