Discovery of novel modulators of metabotropic glutamate receptor subtype-5.
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.
Wang
Bowei
B
Department of Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, 92121, San Diego, CA 92121, USA. bowei_wang@merck.com
Vernier
Jean Michel
JM
Rao
Sara
S
Chung
Janice
J
Anderson
Jeffery J
JJ
Brodkin
Jesse D
JD
Jiang
Xiaohui
X
Gardner
Michael F
MF
Yang
Xiaoqing
X
Munoz
Benito
B
D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
D001583:Benzoxazoles; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate