title: An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.
abstract: 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.
authors.affiliation: Evotec (UK) Ltd, 114 Milton Park, Abingdon, OX14 4SD, UK. stephen.east@evotec.com
authors.forename: Stephen P
authors.initials: SP
authors.lastname: East
authors.forename: Samantha
authors.initials: S
authors.lastname: Bamford
authors.forename: Matthias G A
authors.initials: MG
authors.lastname: Dietz
authors.forename: Christian
authors.initials: C
authors.lastname: Eickmeier
authors.forename: Adam
authors.initials: A
authors.lastname: Flegg
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Gemkow
authors.forename: Ralf
authors.initials: R
authors.lastname: Heilker
authors.forename: Bastian
authors.initials: B
authors.lastname: Hengerer
authors.forename: Adrian
authors.initials: A
authors.lastname: Kotey
authors.forename: Pui
authors.initials: P
authors.lastname: Loke
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schänzle
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Schubert
authors.forename: John
authors.initials: J
authors.lastname: Scott
authors.forename: Mark
authors.initials: M
authors.lastname: Whittaker
authors.forename: Mildred
authors.initials: M
authors.lastname: Williams
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Zawadzki
authors.forename: Kai
authors.initials: K
authors.lastname: Gerlach
mesh_terms: 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
chemical_list: C553344:4-styrylpyrimidin-2-ylamine; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; D013343:Styrenes; C108823:metabotropic glutamate receptor 4