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.
Davydova
N K
NK
Department of Organic Synthesis, Centre of Chemistry of Drugs, Zubovskaya Str. 7, Moscow, Russia. davydova@dmg.genebee.msu.su
Sizova
O S
OS
Vinogradova
S M
SM
L'vov
A I
AI
Glushkov
R G
RG
Yuzhakov
S D
SD
Mashkovskiy
M D
MD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002415:Cats; D003959:Diamines / Q000138:chemical synthesis* / Q000494:pharmacology; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D010420:Pentanes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D003959:Diamines; D010420:Pentanes; C105049:nibentan