Patent Evaluation: Novel 3-Indolyl Thioacetate Derivatives as NMDA Receptor Antagonists

Summary

Novelty: New 3-indolylthioacetate derivatives are disclosed as NMDA antagonists. The compounds are claimed to be useful in treating convulsions, ischaemia, hypoxic or hypoglycaemic conditions and neurodegenerative diseases. They also have an anxiolytic effect.

Biology: Anticonvulsant properties are assessed in vivo by inhibition of quinolinic acid-induced seizures in mice, where the control group has a statistically higher seizure rate than mice administered intracerebroventricularly with the test compound. Anti-epileptic activity is assessed by inhibition of audiogenic convulsion (one hundred and ten decibels for thirty seconds) in mice with similiar results. The anxiolytic effect is measured by blocking the ultrasonic vocalization in rat pups in vivo when removed from the litter, again the two groups show statistical differences.

Chemistry: Synthesis, by conventional methods, of the starting material, the 3,5-dichlorophenylhydrazone of ethyl pyruvate, and of eleven compounds is presented. Characterization is by Mp, IR and NMR. The preferred compound is 2-carboxyethyl-4,6-dichloroindole. A large number of compounds are claimed.