An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.
A high-throughput screening campaign identified 4-((E)-styryl)-pyrimidin-2-ylamine (11) as a positive allosteric modulator of the metabotropic glutamate (mGlu) receptor subtype 4. An evaluation of the structure-activity relationships (SAR) of 11 is described and the efficacy of this compound in a haloperidol-induced catalepsy rat model following oral administration is presented.
East
Stephen P
SP
Evotec (UK) Ltd, 114 Milton Park, Abingdon, OX14 4SD, UK. stephen.east@evotec.com
Bamford
Samantha
S
Dietz
Matthias G A
MG
Eickmeier
Christian
C
Flegg
Adam
A
Ferger
Boris
B
Gemkow
Mark J
MJ
Heilker
Ralf
R
Hengerer
Bastian
B
Kotey
Adrian
A
Loke
Pui
P
Schänzle
Gerhard
G
Schubert
Hans-Dieter
HD
Scott
John
J
Whittaker
Mark
M
Williams
Mildred
M
Zawadzki
Przemyslaw
P
Gerlach
Kai
K
D000284:Administration, Oral; D000494:Allosteric Regulation; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D057166:High-Throughput Screening Assays; D006801:Humans; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
C553344:4-styrylpyrimidin-2-ylamine; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; D013343:Styrenes; C108823:metabotropic glutamate receptor 4