Synthesis and pharmacological properties of 4-piperazino-5-methylthiopyrimidines. Selection of new antiemetic agents

We have synthetized a series of 22 new 4-piperazinopyrimidines bearing a methylthio substituent in the 5 position of the pyrimidine ring. These compounds have been obtained by separation of the isomers formed during nucleophilic attack of the corresponding 2,4,6-trichloropyrimidine by amines. Pharmacological screening has shown that this chemical series displays a very interesting profile, which includes antiemetic, tranquilizing, analgesic, antiserotonin, and musculotropic-spasmolytic properties. We have particularly selected for clinical investigations two compounds with powerful antiemetic activity: 2-methylamino-4-(N-methylpiperazino)-5-methylthio-6-chloropyrimidine and 2-isopropylamino-4-(H-methylpiperazino)-5-methylthio-6-chloropyrimidine.