Benzazoles as allosteric potentiators of metabotropic glutamate receptor 2 (mGluR2): efficacy in an animal model for schizophrenia.
Metabotropic glutamate receptor 2 (mGluR2) has been implicated in a variety of CNS disorders, including schizophrenia. Disclosed herein is the development of a new series of allosteric potentiators of mGluR2. Structure-activity relationship studies in conjunction with pharmacokinetic data led to the discovery of indole 5, which is active in an animal model for schizophrenia.
Govek
Steven P
SP
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA. sgovek@san.rr.com
Bonnefous
Celine
C
Hutchinson
John H
JH
Kamenecka
Theodore
T
McQuiston
Jeffrey
J
Pracitto
Richard
R
Zhao
Lucy X
LX
Gardner
Michael F
MF
James
Joyce K
JK
Daggett
Lorrie P
LP
Rowe
Blake A
BA
Schaffhauser
Hervé
H
Bristow
Linda J
LJ
Campbell
Una C
UC
Rodriguez
Dana E
DE
Vernier
Jean-Michel
JM
D000098:Acetophenones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D015394:Molecular Structure; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000098:Acetophenones; D003432:Cross-Linking Reagents; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D007649:Ketamine