title: In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists.
abstract: The SAR of a series of novel pyrido[3,4-d]pyramid-4-ylamine mGluR1 antagonists is described. The multiple of the unbound K(i) in cerebrospinal fluid necessary to give morphine like analgesic effects in an electromyograph pinch model in rodents is determined and the effect of structure on CNS penetration examined.
authors.affiliation: Drug Discovery Group, Medical Research Council Technology, Mill Hill, London, United Kingdom. simon.mantell@pfizer.com
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mantell
authors.forename: Karl R
authors.initials: KR
authors.lastname: Gibson
authors.forename: Simon A
authors.initials: SA
authors.lastname: Osborne
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Huw
authors.initials: H
authors.lastname: Rees
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dodd
authors.forename: Ben
authors.initials: B
authors.lastname: Greener
authors.forename: Gareth W
authors.initials: GW
authors.lastname: Harbottle
authors.forename: William A
authors.initials: WA
authors.lastname: Million
authors.forename: Cedric
authors.initials: C
authors.lastname: Poinsard
authors.forename: Steven
authors.initials: S
authors.lastname: England
authors.forename: Pauline
authors.initials: P
authors.lastname: Carnell
authors.forename: Alison M
authors.initials: AM
authors.lastname: Betts
authors.forename: Russell
authors.initials: R
authors.lastname: Monhemius
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Prime
mesh_terms: D000818:Animals; D004576:Electromyography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1