Renaissance of dinitroazetidine: novel hybrid energetic boosters and oxidizers.

Nitrogen-oxygen organic materials constitute an important family of multipurpose high-energy materials. However, the preparation of energetic boosters and oxidizers for various civil and space technologies remains a challenging task and such materials usually require special precautions and fine tunability of their functional properties. To find a balance between energy and safety while retaining the oxidizing ability of target energetic materials, novel hybrid organic compounds comprising furoxan and 3,3-dinitroazetidine scaffolds enriched with additional nitro groups were synthesized. The prepared 3-(3,3-dinitroazetidinoyl)-4-nitrofuroxan and 3,3-dinitro-1-(2,2,2-trinitroethyl)azetidine have high nitrogen-oxygen contents (75-79%), positive oxygen balance to CO (up to +10.3%) and good experimental densities (1.75-1.80 g cm-3). A combination of superior detonation performance (D = 8.3-8.5 km s-1 and P = 32-33 GPa) and moderate mechanical sensitivity enables the application potential of these energetic materials as booster explosives or oxidizers. Additionally, their functional properties remain essentially competitive with other oxygen-rich energetic materials (pentaerythritol tetranitrate, ammonium dinitramide, and tetranitratoethane). Hirshfeld surface calculations supported by energy framework plots were also performed to better understand the relationship between the molecular structure and stability/sensitivity. This work unveils novel directions in the construction of balanced energetic boosters and oxidizers for various applications.

Antiaggregant effects of (1,2,5-oxadiazolyl)azasydnone ring assemblies as novel antiplatelet agents.

A series of biheterocyclic assemblies comprising of 1,2,5-oxadiazole and azasydnone scaffolds were synthesized and biologically evaluated as novel nitric oxide (NO)-donor and antiplatelet agents. Depending on functional substituents at the biheterocyclic core, all studied compounds demonstrated good NO-donor profiles releasing NO in a wide range of concentrations (19.2%-195.1%) according to a Griess assay. (1,2,5-Oxadiazolyl)azasydnones showed excellent antiplatelet activity in the case of ADP and adrenaline used as inducers completely suppressing the aggregate formation even at the lowest test concentration of 0.0375 µmol/ml, which is a rather unique feature. Moreover, studied biheterocycles possess a selective mechanism of inhibition of platelet aggregation mediated only by ADP and adrenaline, which are considered to be the main inducers causing thrombus formation. In addition, (1,2,5-oxadiazolyl)azasydnones were found to be completely non-toxic to hybrid endothelial cells EaHy 926. Studies of hydrolytic degradation of the synthesized compounds afforded benzoic acid as a sole detectable decomposition product, which is considered advantageous in drug design. Therefore, (1,2,5-oxadiazolyl)azasydnones represent a novel class of promising drug candidates with improved antiplatelet profile and reduced toxicity enabling their huge potential in medicinal chemistry and drug design.

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors.

Nitric oxide (NO) is a key signaling molecule that acts in various physiological processes such as cellular metabolism, vasodilation and transmission of nerve impulses. A wide number of vascular diseases as well as various immune and neurodegenerative disorders were found to be directly associated with a disruption of NO production in living organisms. These issues justify a constant search of novel NO-donors with improved pharmacokinetic profiles and prolonged action. In a series of known structural classes capable of NO release, heterocyclic NO-donors are of special importance due to their increased hydrolytic stability and low toxicity. It is no wonder that synthetic and biochemical investigations of heterocyclic NO-donors have emerged significantly in recent years. In this review, we summarized recent advances in the synthesis, reactivity and biomedical applications of promising heterocyclic NO-donors (furoxans, sydnone imines, pyridazine dioxides, azasydnones). The synthetic potential of each heterocyclic system along with biochemical mechanisms of action are emphasized.

Straightforward Access to the Nitric Oxide Donor Azasydnone Scaffold by Cascade Reactions of Amines.

A novel one-pot cascade method for the assembly of valuable NO-donor azasydnone scaffold has been developed. The construction strategy involves a diazotization/azo coupling/elimination/double rearrangement cascade sequence of readily available amines. The current protocol enables the generation of a diverse array of azasydnones, including previously hardly accessible heteroaryl substituted azasydnones (25 examples, 70-97 % yield) with a good functional group tolerance under very mild conditions. Preliminary NO-releasing studies revealed an ability of azasydnones to produce NO in a wide range of concentrations. This method provides a new approach to nitrogen-oxygen heterocycles with potential applications in medicine and material science.