Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5.
The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in numerous neuropsychiatric disorders including addiction. We have discovered that the rigid diaryl alkyne template, derived from the potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), can serve to guide the design of novel quinoline analogues and pharmacophore optimization has resulted in potent mGluR5 noncompetitive antagonists (EC(50) range 60-100 nM) in the quinoline series.
Zhang
Peng
P
Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Zou
Mu-Fa
MF
Rodriguez
Alice L
AL
Conn
P Jeffrey
PJ
Newman
Amy Hauck
AH
D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry*; D001921:Brain / Q000166:cytology; D002460:Cell Line; D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
D052160:Benzothiazoles; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; C005465:benzothiazole
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