Research On Synthesis And Antitussive Activity Of Dropropizine's Derivatives

Levodropropizine(LD), a new kind of peripheral antitussive,can be used to treat cough by controlling the sensory neuropeptide released from bronchus' c-fibres. Levodropropizine has the same antitussive activity as dropropizine, but with less side effect than its racemate(dropropizine). Based on our research on the molecule structures of various kinds of antitussives , LD and its reported derivatives, our research on the mechanism of cough reflex, the effect of c-fibres on respiratory system,and the principle of bioisosterism ,with the racemate(dropropizine) of LD's as a lead compound ,.through substituting the 1-hydroxy group of the racemate of LD, and by way of structure optimization,we have designed and synthesized eleven unreported compounds. These unreported compounds have been confirmed with the method of 1H-NMR, MS spectrum. With the nineteen compounds synthesized by others and the eleven novel compounds synthesized by the author ,totally thirty compounds ,we have finished the initial pharmacology experiment for choosing the drugs for diseases of respiratory system, and .it was indicated that n-Propylamine dropropizine had greater effect on cough than LD,while the other compounds with Amino groups as substitutes had comparable activity with LD as antitussive. Compared with the control group, the compounds with alkoxy and aryloxy as substitutes have shown some antitussive activity,but their activity was obviously less than that of amino-groups-substituted compands. Meanwhile,it was also discovered that among the thirty compounds , the EDT50 of the higher dose group was longer than that of the lower dose group, only with the number11 compound as an exception.