THE STUDY OF THE STRUCTURE - ANTIARRHYTHMIC ACTIVITY RELATIONSHIP AMONGN-[2-(1-ADAMANTYLAMINO)-2-OXOETHYL]-N-( ω-AMINOALKYL) AMIDES OF NITROBENZOIC ACIDS

The original selective blocker of voltage-transmembrane potassium channels pharmacological drug cardiocyclide (N-[2-(dicyclohexylamino)- 2-oxoethyl]-N-[3-(diethylamino)propyl]-4-nitrobenzoic carboxamide hydrocloride) has been earlier synthesized and pharmacologically studied in the State Foundation Institute of Pharmacology of RAMS. In the development of these research the structure- antiarrhythmic activity relationship among N-[2-(1-adamantylamino)-2-oxoethyl]-N-(ω-aminoalkyl) amides of nitrobenzoic acids has been studied. It was hypothesized that new compounds required the special pharmacophoric elements providing the activity. The dialkylamino group has the significant influence on the activity. The extension of the chain connecting the pharmacophore centers by one methylene leads to the increase of the activity. Moreover, the aminoacetic acid derivatives are more active and more toxic than the α-aminopropionic acid derivatives. The position of the nitro group in the benzene ring has the significant influence on the antiarrhythmic activity of the compounds. The studies revealed the most active compound to be N-[2-(adamantylamino)-2-oxoethyl]-N-[3-(diethylamino)propyl]-4-nitrobenzoic carboxamide hydrocloride which is comparable in its antiarrhythmic activity with prototype of cardiocyclide but in contrast with the latter, does not have the phlebotoxic action.