title: 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats.
abstract: Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu(5) using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Felts
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Lindsley
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Lamb
authors.forename: Alice L
authors.initials: AL
authors.lastname: Rodriguez
authors.forename: Usha N
authors.initials: UN
authors.lastname: Menon
authors.forename: Satyawan
authors.initials: S
authors.lastname: Jadhav
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Jones
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Emmitte
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D001798:Blood Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate