(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.
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.
Collado
Iván
I
Lilly, SA, Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. collado_ivan@lilly.com
Pedregal
Concepción
C
Bueno
Ana Belén
AB
Marcos
Alicia
A
González
Rosario
R
Blanco-Urgoiti
Jaime
J
Pérez-Castells
Javier
J
Schoepp
Darryle D
DD
Wright
Rebecca A
RA
Johnson
Bryan G
BG
Kingston
Ann E
AE
Moher
Eric D
ED
Hoard
David W
DW
Griffey
Kelly I
KI
Tizzano
Joseph P
JP
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
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