Fused thiazolyl alkynes as potent mGlu5 receptor positive allosteric modulators.

Abstract A new series of potent fused thiazole mGlu 5 receptor positive allosteric modulators ( PAMs ) ( 10 , 11 and 27–31 ) are disclosed and details of the SAR and optimization are described. Optimization of alkynyl thiazole 9 ( Lu AF11205 ) led to the identification of potent fused thiazole analogs 10b , 27a , 28j and 31d . In general, substituted cycloalkyl, aryl and heteroaryl carboxamides, and carbamate analogs are mGlu 5 PAMs , whereas smaller alkyl carboxamide, sulfonamide and sulfamide analogs tend to be mGlu 5 negative allosteric modulators ( NAMs ).