title: Structure-activity relationships of novel non-competitive mGluR1 antagonists: a potential treatment for chronic pain.
abstract: A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.
authors.affiliation: Pfizer Global Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK. dafydd.owen@pfizer.com
authors.forename: Dafydd R
authors.initials: DR
authors.lastname: Owen
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dodd
authors.forename: Simon
authors.initials: S
authors.lastname: Gayton
authors.forename: Ben S
authors.initials: BS
authors.lastname: Greener
authors.forename: Gareth W
authors.initials: GW
authors.lastname: Harbottle
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mantell
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Simon A
authors.initials: SA
authors.lastname: Osborne
authors.forename: Huw
authors.initials: H
authors.lastname: Rees
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Ringer
authors.forename: Margarita
authors.initials: M
authors.lastname: Rodriguez-Lens
authors.forename: Graham F
authors.initials: GF
authors.lastname: Smith
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002908:Chronic Disease; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011719:Pyrazines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid