Design of a novel cognitive enhancer (8S, 10aS)-8-carbamoyl-1,2,3,6,7,8,9,10a-octahydro-5H,10H-pyrrolo[1,2-a][1,4]diazocin-5,10-dione

A new cognitive enhancer (8S, 10aS)-8-carbamoyl-1,2,3,6,7,8,9,10a-octahydro-5H,10H-pyrrolo[1,2-a][1,4]diazocin-5,10-dione (3) has been designed based on the approach consisting of two steps: 1) “obligatory” replacement of histidine with glutamine in TRH; 2) the application of conformational constraints for putative bioactive conformation of [Gln2]-TRH. 3 reversed on 100% electroconvulsive shock-induced amnesia at doses of 0.1 and 1.0 mg/kg and on 83% scopolamine-induced amnesia at a dose of 1 mg/kg, using passive avoidance test.