title: 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators.
abstract: The synthesis and structure-activity relationship (SAR) of a novel series of 3-(imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers, derived from a high throughput screening (HTS), are described. Subsequent optimization led to identification of potent, metabolically stable and orally available mGluR2 positive allosteric modulators (PAMs).
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. Lei.Zhang3@pfizer.com
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Rogers
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Duplantier
authors.forename: Stanley F
authors.initials: SF
authors.lastname: McHardy
authors.forename: Ivan
authors.initials: I
authors.lastname: Efremov
authors.forename: Helen
authors.initials: H
authors.lastname: Berke
authors.forename: Weimin
authors.initials: W
authors.lastname: Qian
authors.forename: Andy Q
authors.initials: AQ
authors.lastname: Zhang
authors.forename: Noha
authors.initials: N
authors.lastname: Maklad
authors.forename: John
authors.initials: J
authors.lastname: Candler
authors.forename: Angela C
authors.initials: AC
authors.lastname: Doran
authors.forename: John T
authors.initials: JT
authors.lastname: Lazzaro
authors.forename: Alan H
authors.initials: AH
authors.lastname: Ganong
mesh_terms: D000284:Administration, Oral; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004987:Ethers / Q000737:chemistry*; D006801:Humans; D008861:Microsomes / Q000187:drug effects; D008956:Models, Chemical; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry*; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D053961:Azabicyclo Compounds; D001562:Benzimidazoles; D004987:Ethers; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2