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. (C) 2009 Elsevier Ltd. All rights reserved.