title: (2S,1'S,2'R,3'R)-2-(2'-Carboxy-3'-hydroxymethylcyclopropyl) glycine is a highly potent group 2 and 3 metabotropic glutamate receptor agonist with oral activity.
abstract: The asymmetric synthesis and biological activity of (2S,1'S,2'R,3'R)-2-(2'-carboxy-3'-hydroxymethylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.
authors.affiliation: Lilly, SA, Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. collado_ivan@lilly.com
authors.forename: Iván
authors.initials: I
authors.lastname: Collado
authors.forename: Concepción
authors.initials: C
authors.lastname: Pedregal
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Bueno
authors.forename: Alicia
authors.initials: A
authors.lastname: Marcos
authors.forename: Rosario
authors.initials: R
authors.lastname: González
authors.forename: Jaime
authors.initials: J
authors.lastname: Blanco-Urgoiti
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-Castells
authors.forename: Darryle D
authors.initials: DD
authors.lastname: Schoepp
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Wright
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Johnson
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kingston
authors.forename: Eric D
authors.initials: ED
authors.lastname: Moher
authors.forename: David W
authors.initials: DW
authors.lastname: Hoard
authors.forename: Kelly I
authors.initials: KI
authors.lastname: Griffey
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Tizzano
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D005239:Fear; D005998:Glycine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C482218:2-(2'-carboxy-3'-hydroxymethylcyclopropyl)glycine; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D000242:Cyclic AMP; D005998:Glycine