Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists.
Rational replacement of the alkyne linker of mGluR5 antagonist MPEP gave 7-arylquinolines. SAR optimization gave an orally active compound with high affinity for the MPEP binding site.
Milbank
Jared B J
JB
Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. Jared.Milbank@Pfizer.com
Knauer
Christopher S
CS
Augelli-Szafran
Corinne E
CE
Sakkab-Tan
Annette T
AT
Lin
Kristin K
KK
Yamagata
Koji
K
Hoffman
Jennifer K
JK
Zhuang
Nian
N
Thomas
John
J
Galatsis
Paul
P
Wendt
John A
JA
Mickelson
John W
JW
Schwarz
Roy D
RD
Kinsora
Jack J
JJ
Lotarski
Susan M
SM
Stakich
Korana
K
Gillespie
Kristen K
KK
Lam
Wing W
WW
Mutlib
Abdul E
AE
D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine