2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl) pyridine: a highly potent, orally active, metabotropic glutamate subtype 5 (mGlu5) receptor antagonist.
Structure-activity relationship studies on 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile 2 led to the discovery of 2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl)pyridine (10)-a highly potent and selective mGlu5 receptor antagonist with good brain penetration and in vivo receptor occupancy in rat and cross-species oral bioavailability.
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA.
Dehua
D
Huang
Steve F
SF
Poon
Deborah F
DF
Chapman
Janice
J
Chung
Merryl
M
Cramer
Thomas S
TS
Reger
Jeffrey R
JR
Roppe
Lida
L
Tehrani
Nicholas D P
ND
Cosford
Nicholas D
ND
Smith
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry / Q000493:pharmacokinetics*; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics*
C497737:2-(2-(3-(pyridin-3-yloxy)phenyl)-2H-tetrazol-5-yl)pyridine; C497738:3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile; D014151:Anti-Anxiety Agents; D009570:Nitriles; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013777:Tetrazoles