Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides as potent, orally available mGlu1 receptor enhancers.
Small molecule mGluR1 enhancers, which are 9H-xanthene-9-carboxylic acid [1,2,4]oxadiazol-3-yl- and (2H-tetrazol-5-yl)-amides, have been previously reported. Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides with improved pharmacokinetic properties have been designed and synthesized as useful pharmacological tools for the study of the physiological roles mediated by mGlu1 receptors. The synthesis and the structure-activity relationship of this class of positive allosteric modulators of mGlu1 receptors will be discussed in detail.
Vieira
Eric
E
Pharma Division, Discovery Research, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland.
Huwyler
Jörg
J
Jolidon
Synèse
S
Knoflach
Frédéric
F
Mutel
Vincent
V
Wichmann
Jürgen
J
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1