Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists

The identification of structurally novel analogues of ketamine and phencyclidine (PCP), as NMDA receptor antagonists, with low to moderate potency at GluN2A and GluN2B receptors is discussed. In particular, some examples, such as compounds 6 and 10, shows decreased calculated lipophilicity, when compared to PCP, while retaining moderate activity. Moreover, the germinal aryl amino substituted lactam ring, as exemplified in compounds 7–10 and 11–13, constitutes a novel scaffold with potential application in the design of biologically active compounds.

Graphical abstractThe identification of structurally novel analogues of ketamine and phencyclidine (PCP), as NMDA receptor antagonists, with low to moderate potency at GluN2A and GluN2B receptors is discussed. In particular, some examples, such as compounds 6 and 10, show decreased calculated lipophilicity, when compared to PCP, while retaining moderate activity. Moreover, the germinal aryl amino substituted lactam ring, as exemplified in compounds 7–10 and 11–13, constitutes a novel scaffold with potential application in the design of biologically active compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide