New synthesis of substituted 2-carboxyindole derivatives: Versatile introduction of a carbamoylethynyl moiety at the C-3 position

A novel series of 3-carbamoylethynyl-2-carboxyindoles, antagonists acting a t the strychnine-insensitive glycine binding site associated with the NMDA receptor, has been synthesised. This new versatile approach involves the in troduction of a 2-chloroethenyl moiety in position C-3 with subsequent deri vatisation of the terminal carboxyl group, followed by an unusual eliminati on of HCl to afford the ethynyl functionality. This novel series of glycine antagonists was evaluated in terms of in vitro affinity at the glycine bin dings site and the most potent compound was tested in vivo in the NMDA-indu ced convulsions model in mice.