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.
D000818:Animals; D000932:Antiemetics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001066:Appetite / Q000187:drug effects; D004285:Dogs; D007536:Isomerism; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D012702:Serotonin Antagonists; D013035:Spasm / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D014839:Vomiting / Q000517:prevention & control
D000932:Antiemetics; D010879:Piperazines; D011743:Pyrimidines; D012702:Serotonin Antagonists; D013440:Sulfides; D001058:Apomorphine