A method for designing conformationally restricted analogues based on allylic strain: synthesis of a novel class of noncompetitive NMDA receptor antagonists having the acrylamide structure.

A series of conformationally restricted analogues of milnacipran, a weak NMDA receptor antagonist, were designed by a method based on allylic strain. The conformational analysis study showed that the allylic-strain-based conformational restriction indeed occurred and that the affinity for the NMDA receptor was efficiently improved by the conformational restriction.