3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators.
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).
Zhang
Lei
L
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. Lei.Zhang3@pfizer.com
Rogers
Bruce N
BN
Duplantier
Allen J
AJ
McHardy
Stanley F
SF
Efremov
Ivan
I
Berke
Helen
H
Qian
Weimin
W
Zhang
Andy Q
AQ
Maklad
Noha
N
Candler
John
J
Doran
Angela C
AC
Lazzaro
John T
JT
Ganong
Alan H
AH
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
D053961:Azabicyclo Compounds; D001562:Benzimidazoles; D004987:Ethers; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2