Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions.

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds L and L, with L inducing temporary bradycardia and hypotension specifically in female rats, and L causing significant blood pressure reduction followed by rebound in females compared to milder effects in males.

Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine-1,5-Benzodiazepine Hybrids.

Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, have long interested scientists due to their medicinal uses and infamous toxicity which has limited the clinical application of the native compound. Alkaloid lappaconitine extracted from various and species has displayed extensive bioactivities and active ongoing research to reduce its adverse effects. A convenient route to construct hybrid molecules containing diterpenoid alkaloid lappaconitine and 3-1,5-benzodiazepine fragments was proposed.

Investigation of 1,4-Substituted 1,2,3-Triazole Derivatives as Antiarrhythmics: Synthesis, Structure, and Properties.

Here, we investigated the reaction of 1,3-dipolar cycloaddition of 1,3-diazido-2-nitro-2- azapropane (DANP) to propargyl alcohol over a copper-based catalyst and identified the optimum reaction conditions that enable the synthesis of 2-nitro-1,3-bis(4,4'-dihydroxymethyl)-1,2,3-triazolyl-2-azapropane () in more than 84% yield. The reaction between DANP, 1,5-diazido-3-nitrazapentane, and phenylacetylene produced the respective 1,2,3-triazole derivatives in 83% and 71% yields, respectively. The structures of the resultant compounds were validated by infrared and NMR spectroscopies and elemental analysis.

Natural Products as a Source of Antiarrhythmic Drugs.

Throughout the development of medicine, the spotlight has been held by the search for new drugs blocking different types of arrhythmia. In the past decade, much attention was given to the selection of active antiarrhythmic substances from plant material. It has been shown that these compounds have a good antiarrhythmic effect, and their chemical modifications substantially increase their major effects while adding other beneficial pharmacological properties.

Lappaconitine: influence of halogen substituent on the antiarrhythmic activity.

The current paper presents research results related to antiarrhythmic activity of halogen-containing derivatives of lappaconitine. Lappaconitine derivatives with iodine, chlorine or bromine substituting the anthranilate moiety at C-5` position were shown in vivo and in vitro to exhibit a more (Br, I) or less (Cl) pronounced antiarrhythmic activity in the models of calcium chloride- and adrenaline-induced arrhythmias as compared with the reference compound lappaconitine. The intensity of antiarrhythmic action depending on halogen substituent was found to be expressed by the following order: Cl < I < Br.