Cyclohexenyl- and dehydropiperidinyl-alkynyl pyridines as potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists.
Structure-activity relationship studies leading to the discovery of novel mGlu5 receptor antagonists are described. These compounds show high in vitro potency, have good in vivo receptor occupancy, and a reasonable intravenous pharmacokinetic profile.
Chua
Peter C
PC
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2 3535 General Atomics Court, San Diego, CA 92121, USA. pchua@cylenepharma.com
Nagasawa
Johnny Y
JY
Bleicher
Leo S
LS
Munoz
Benito
B
Schweiger
Edwin J
EJ
Tehrani
Lida
L
Anderson
Jeffrey J
JJ
Cramer
Merryl
M
Chung
Janice
J
Green
Mitchell D
MD
King
Chris D
CD
Reyes-Manalo
Grace
G
Cosford
Nicholas D P
ND
D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate