Enecadin

Enecadin was an investigational new drug developed as a neuroprotectant for use following cerebral infarction. It was originally discovered by Nippon Shinyaku and later out-licensed to Schering in 1999.
Enecadin exerts its neuroprotective effects by blocking voltage-gated sodium and calcium channels, which play key roles in excitotoxicity during ischemic injury. By limiting pathological ion influx, the compound was shown to preserve neuronal integrity in experimental models of stroke, spinal cord injury, and retinal ischemia.
The drug advanced to Phase II clinical trials for acute ischemic stroke, but development was discontinued after the trial was terminated.

Synthesis

Patent:
A Claisen-Schmidt reaction between p-fluoroacetophenone and diethyl carbonate gives ethyl 3--3-oxopropanoate . Treatment with acetamidine hydrochloride leads to the formation of 4--6-hydroxy-2-methylpyrimidine . Halogenation with phosphoryl chloride led to 4-chloro-6--2-methylpyrimidine . Williamson ether synthesis with 5-piperidino-1-pentanol completed the synthesis of Enecadin.