A novel class of AMPA receptor allosteric modulators. Part 1: Design, synthesis, and SAR of 3-aryl-4-cyano-5-substituted-heteroaryl-2-carboxylic acid derivatives

The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4- tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ( 6a) are described. The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4- tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ( 6a) are described. SAR studies at the thioether moiety indicated that substitution at this position was mandatory and better potency was achieved with small groups.