Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones

Anthony B Pinkerton; Rowena V Cube; John H Hutchinson; Blake A Rowe; Hervé Schaffhauser; Xiumin Zhao; Lorrie P Daggett; Jean-Michel Vernier

doi:10.1016/j.bmcl.2004.08.020

Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5329-32. doi: 10.1016/j.bmcl.2004.08.020.

Authors

Anthony B Pinkerton¹, Rowena V Cube, John H Hutchinson, Blake A Rowe, Hervé Schaffhauser, Xiumin Zhao, Lorrie P Daggett, Jean-Michel Vernier

Affiliation

¹ Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. anthony_pinkerton@merck.com

PMID: 15454221
DOI: 10.1016/j.bmcl.2004.08.020

Abstract

We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC(50)=93nM, 128% potentiation).

MeSH terms

Acetophenones / chemical synthesis*
Acetophenones / chemistry
Acetophenones / pharmacology
Allosteric Regulation
Receptors, Metabotropic Glutamate / agonists*
Stereoisomerism
Structure-Activity Relationship
Tetrazoles / chemical synthesis*
Tetrazoles / chemistry
Tetrazoles / pharmacology

Substances

Acetophenones
Receptors, Metabotropic Glutamate
Tetrazoles
metabotropic glutamate receptor 2