Discovery of novel modulators of metabotropic glutamate receptor subtype-5

Bowei Wang; Jean Michel Vernier; Sara Rao; Janice Chung; Jeffery J Anderson; Jesse D Brodkin; Xiaohui Jiang; Michael F Gardner; Xiaoqing Yang; Benito Munoz

doi:10.1016/j.bmc.2003.10.021

Discovery of novel modulators of metabotropic glutamate receptor subtype-5

Bioorg Med Chem. 2004 Jan 2;12(1):17-21. doi: 10.1016/j.bmc.2003.10.021.

Authors

Bowei Wang¹, Jean Michel Vernier, Sara Rao, Janice Chung, Jeffery J Anderson, Jesse D Brodkin, Xiaohui Jiang, Michael F Gardner, Xiaoqing Yang, Benito Munoz

Affiliation

¹ Department of Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, 92121, San Diego, CA 92121, USA. bowei_wang@merck.com

PMID: 14697765
DOI: 10.1016/j.bmc.2003.10.021

Abstract

A series of potent and selective mGluR5 antagonists were synthesized and evaluated in vitro and in vivo. It was found that a pyridyl functionality is a potential replacement for acetonitrile in the lead structure, with 2-pyridyl being most favored. Additionally, the benzoxazole moiety could also be replaced by other heterobicyclic rings such as imidazothiazole.

MeSH terms

Animals
Benzoxazoles / chemistry
Benzoxazoles / pharmacology*
Biological Availability
Excitatory Amino Acid Antagonists / chemistry*
Excitatory Amino Acid Antagonists / pharmacology
Rats
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / physiology

Substances

Benzoxazoles
Excitatory Amino Acid Antagonists
Grm5 protein, rat
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate