Abstract
In a study of structure-activity relationship in antitussive agents, a working hypothesis has been presented that the introduction of a piperidino group into a compound showing any actions on the central nervous system, can produce antitussive activity if the activity has been latent, or strengthen it if such activity is already manifest (1, 2). In the previous study, antitussive activity of 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide (264-CE, Hexacol®) had been investigated and it was found that the activity of the drug was 1/4 to 1/3 as potent as that of codeine (3).
Therefore, in order to strengthen the antitussive activity, 2-allyloxy-4-chloro-N-(2-piperidinoethyl) benzamide (abbreviated as 264CP) in which a piperidino group was introduced in stead of a diethylamino group in the structure of 264CE was synthesized. Other 6 compounds including amino groups such as pyrrolidino, morpholino, piperazino, dimethylamino and primary amino groups in stead of a diethylamino group, and a trifluoromethyl group in stead of chlor (2-allyloxy-4-trifluoromethyl-N-(2-diethylaminoethyl) benzamide, 305-CE) were also synthesized for testing their antitussive activities.
In the present experiment, the antitussive actions and other pharmacological actions of these 7 compounds, especially those of 264CP, have been compared with those of 264-CE.
