Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 3: Identification and biological activity of indanone containing mGlu2 receptor potentiators.
We have identified and synthesized a series of phenyl-tetrazolyl and 4-thiopyridyl indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation, as well as PK properties, led to the discovery of 28 (EC50=186 nM), which displayed activity in a rodent model for schizophrenia.
Pinkerton
Anthony B
AB
Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. anthony_pinkerton@merck.com
Cube
Rowena V
RV
Hutchinson
John H
JH
James
Joyce K
JK
Gardner
Michael F
MF
Rowe
Blake A
BA
Schaffhauser
Hervé
H
Rodriguez
Dana E
DE
Campbell
Una C
UC
Daggett
Lorrie P
LP
Vernier
Jean-Michel
JM
D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D007189:Indans / Q000493:pharmacokinetics / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship
D007189:Indans; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2