Discovery and SAR studies of novel GlyT1 inhibitors.
Inhibition of the glycine transporter GlyT1 is a potential strategy for the treatment of schizophrenia. A novel series of GlyT1 inhibitors and their structure-activity relationships (SAR) are described. Members of this series are highly potent and selective transport inhibitors which are shown to elevate glycine levels in cerebrospinal fluid.
Walter
Magnus W
MW
Lilly Research Laboratories, Eli Lilly and Company, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK. magnus.walter@lilly.com
Hoffman
Beth J
BJ
Gordon
Kimberly
K
Johnson
Kirk
K
Love
Patrick
P
Jones
Matthew
M
Man
Teresa
T
Phebus
Lee
L
Reel
Jon K
JK
Rudyk
Helene C
HC
Shannon
Harlan
H
Svensson
Kjell
K
Yu
Hong
H
Valli
Matthew J
MJ
Porter
Warren J
WJ
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D050487:Glycine Plasma Membrane Transport Proteins; C493266:Slc6a9 protein, rat