Synthesis and antifibrillatory activity of nibentan and its analogues

A series of 1,5-diaminopentane derivatives, structurally related to nibentan, was synthesized and tested for antifibrillatory activity. Improved modifications of some known chemical syntheses were proposed. (±)-N-[5-(Diethylamino)-1-(4-nitrophenyl)pentyl]-benzamide hydrochloride, (±)-N-[5-(diethylamino)-1-(4-nitrophenyl)pentyl]-4-nitrobenzamide hydrochloride and (±)-N-[5-(diethylamino)-1-(4-hydroxyphenyl)pentyl]-4-nitrobenzamide hydrochloride were more potent than nibentan and possessed a longer duration of action (up to 5 h in comparison with 60–90 min for nibentan). The antifibrillatory activity of (±)-N-[5-(diethylamino)-1-(4-methoxyphenyl)pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-sotalol and sematilide.