Research On Synthesis And Antitussive Activity Of Lveodropropizine And Its Derivatives

Levodropropizine-as a new chiral antitussive drug that has been produced and used in clinic therapy in several countries, is much more selective and lower undesired side-effects than other antitussive drugs that were used in clinic at present. It hasn't been imported and produced in domestic market. So it is very profit to both society and economy to research synthesis of this drug. According to our producing conditions, we adopted the aniline diethanolamine as the raw material to synthesize it. The N-Phenylpiperazine was prepared by mixing aniline and diethanolamine in the presence of A12O3 and concentrated hydrochloric acid. The mixture was heated to 220. The epichlorohydrin was hydrolyzed to 3-chloro-l,2-propanediol in sulfuric aqueous solution at 80, then the dropropizine was obtained by combining the N-Phenylpiperazine and 3-chloro-l,2-propanediol. The resolution of dropropizine was carried out by treating it with L-(+)-tartaric acid in aqueous medium to give Levodropropizine. In order to find more potent new drug molecule and providing more information about this type substance to analysis the Q-SAR, we designed some novel molecules according to the principle of isostere. The target molecules were synthesized and identified by spectrum methods. The preliminary antitusive activity of these target molecules was tested on mice, the result suggested that all derivatives were similar to that of levodropropizine,1 -propylamio-3-(4-phenyl-1 -piperazinyl)-2-propanol(CUMS-002) shows better activity .