Alkyl diphenylacetyl, 9H-xanthene- and 9H-thioxanthene-carbonyl carbamates as positive allosteric modulators of mGlu1 receptors.
Starting from the random-screening hit 1a, a series of alkyl diphenylacetyl, 9H-xanthene- and 9H-thioxanthene-carbonyl carbamates 1 has been prepared. These derivatives turned out to be selective positive allosteric modulators of mGlu1 receptors. These compounds do not directly activate mGlu1 receptors but markedly potentiate agonist stimulated responses, increasing potency and maximum efficacy.
Wichmann
Jürgen
J
Pharmaceuticals Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd., Grenzachestr. 124, CH-4070 Basel, Switzerland. juergen.wichmann@roche.com
Bleicher
Konrad
K
Vieira
Eric
E
Woltering
Thomas
T
Knoflach
Frédéric
F
Mutel
Vincent
V
D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004594:Electrophysiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism*; D013892:Thioxanthenes / Q000737:chemistry / Q000494:pharmacology*; D014966:Xanthenes / Q000737:chemistry / Q000494:pharmacology*
D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; D013892:Thioxanthenes; D014966:Xanthenes; C104077:metabotropic glutamate receptor type 1