Targeting NMDA with functionalized adamantanes

Memantine, an adamantane derivative initially developed by Eli Lilly as an antidiabetic agent, is recognized as a moderate non-competitive NMDA receptor antagonist that has been initially approved for a therapeutic use against Alzheimer's disease. Preclinical evidence for its mode of action is based on minimizing excitotoxicity related to calcium influx. Recently, fluorinated analogs have been investigated to take advantage of this peculiar property. A radiofluorinated analog has also been described allowing to visualize its distribution in vivo. This recent work follow up on earlier reports for Fluoromemantine.

In the course of our investigations on the fluorination of side chains of adamantane, we found out that the proposed path to fluoromemantine leads to a mixture of compounds.

We have thus revisited the synthetic access to fluoromemantine and we will provide evidences of our structural assessment based on convergent analytical data.