title: Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 2: 4-thiopyridyl acetophenones as non-tetrazole containing mGlu2 receptor potentiators.
abstract: We have identified and synthesized a series of 4-thiopyridyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward replacement of the tetrazole in the initial lead led to the discovery of 16 (EC(50)=340 nM), which showed improved brain penetration over the initial lead.
authors.affiliation: Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. anthony_pinkerton@merck.com
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Pinkerton
authors.forename: Rowena V
authors.initials: RV
authors.lastname: Cube
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Joyce K
authors.initials: JK
authors.lastname: James
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gardner
authors.forename: Hervé
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Blake A
authors.initials: BA
authors.lastname: Rowe
authors.forename: Lorrie P
authors.initials: LP
authors.lastname: Daggett
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vernier
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000378:metabolism*; D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013777:Tetrazoles
chemical_list: D000098:Acetophenones; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; D013777:Tetrazoles; C108822:metabotropic glutamate receptor 2