Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor.
Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies.
Tresadern
Gary
G
Research Informatics, Johnson & Johnson, Pharmaceutical Research & Development, Janssen-Cilag S.A., Calle Jarama 75, Poligono Industrial, Toledo 45007, Spain. gtresade@its.jnj.com
Cid
Jose María
JM
Macdonald
Gregor J
GJ
Vega
Juan Antonio
JA
de Lucas
Ana Isabel
AI
García
Aránzazu
A
Matesanz
Encarnación
E
Linares
María Lourdes
ML
Oehlrich
Daniel
D
Lavreysen
Hilde
H
Biesmans
Ilse
I
Trabanco
Andrés A
AA
D000494:Allosteric Regulation; D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
D007093:Imidazoles; D011725:Pyridines; D011728:Pyridones; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C029899:imidazole