Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems

1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability

Novel energetic CNO oxidizer: Pernitro-substituted pyrazolyl-furazan framework

There is a need for dense energetic oxidizers whose composition is restricted to carbon, hydrogen, nitrogen and oxygen atoms as chlorine-free alternative to current oxidizers of energetic materials such as explosives, propellants and pyrotechnics. High nitrogen heterocyclic frameworks containing trinitromethyl units are an attractive and increasingly important class of oxygen-rich compounds. Herein, for the first time, a synthetic method has been developed for the preparation of a new (pyrazole-3-yl)furazan framework bearing a nitro group in the furazan ring. From this framework, 3-nitro-4-(4-nitro-1-(trinitromethyl)-1H-pyrazol-3-yl)furazan (15) and 3-(3,4-dinitro-1-(trinitromethyl)-1H-pyrazol-5-yl)-4-nitrofurazan (16) have been produced. The combination of positive enthalpy of formation, high density, favorable physical and thermal properties, and reasonable sensitivity with the promising theoretical energetic performance of these oxygen-rich compounds offers materials not only of fundamental interest, but also for potential practical applications, for example, as promising candidates to new environmentally benign rocket propellants

Adamantyl-ureas with pyrazoles substituted by fluoroalkanes as soluble epoxide hydrolase inhibitors

A series of soluble epoxide hydrolase (sEH) inhibitors containing halogenated pyrazoles was developed. Inhibition potency of the obtained compounds ranges from 0.8 to 27.5 nM. 1-Adamantyl-3-[(4,5-dichloro-1-methyl-1Н-pyrazol-3-yl)methyl]urea (3f, IC50 = 0.8 nM) and 1-[(Adamantan-1-yl)methyl]-3-[(4,5-dichloro-1-methyl-1Н-pyrazol-3-yl)methyl]urea (4f, IC50 = 1.2 nM) were found to be the most potent sEH inhibitors within the described series

Novel energetic furazans containing isomeric N-(azoxy)-dinitropyrazole moieties: Synthesis, characterization and comparison of properties

Novel energetic furazans 3a–3c and 4a–4c containing isomeric (3,4-dinitro-1H-pyrazol-1-yl)-NNO-azoxy and (3,5-dinitro-1H-pyrazol-1-yl)-NNO-azoxy moieties have been obtained. A synthetic approach to aminofurazans 3a and 4a involves the reaction of 1-amino-3,4-dinitro-1H-pyrazole or 1-amino-3,5-dinitro-1H-pyrazole with 2,2,2-trifluoro-N-(4-nitrosofurazan-3-yl)acetamide and dibromoisocyanuric acid, followed by removal of the trifluoroacetyl group. Transformations of the amino group in aminofurazans 3a and 4a gave the corresponding nitro (3b, 4b) and azo (3c, 4c) substituted furazans. The compounds synthesized exhibit high experimental enthalpies of formation (2093–2847 kJ·kg−1), good thermal stabilities (onset decomposition temperatures 203–228 °C), acceptable densities (1.78–1.87 g·cm−3) and high detonation parameters (detonation velocities D = 8.71–8.99 km s−1, detonation pressures p = 33.9–38.7 GPa). Nitro substituted furazans 3b, 4b and azo substituted furazans 3c, 4c have been evaluated as effective energetic fillers for solid composite propellants, providing specific impulse values 9–11 s higher than similar formulations based on RDX and HMX, and 4–6 s higher than similar formulations based on CL-20

A Direct Approach to a 6‑Hetarylamino[1,2,4]triazolo[4,3‑<i>b</i>][1,2,4,5]tetrazine Library

The synthesis of 6-hetarylamino­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines is reported. The functionalized secondary amines were constructed via a K₂CO₃-mediated S_NAr reaction of weakly basic hetarylamines with 3-(3,5-dimethylpyrazol-1-yl)­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines, which allowed displacement 3,5-dimethylpyrazolyl leaving group. Significantly, the reaction exhibited a broad substrate scope and proceeded in good yields

A Direct Approach to a 6‑Hetarylamino[1,2,4]triazolo[4,3‑<i>b</i>][1,2,4,5]tetrazine Library

The synthesis of 6-hetarylamino­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines is reported. The functionalized secondary amines were constructed via a K₂CO₃-mediated S_NAr reaction of weakly basic hetarylamines with 3-(3,5-dimethylpyrazol-1-yl)­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines, which allowed displacement 3,5-dimethylpyrazolyl leaving group. Significantly, the reaction exhibited a broad substrate scope and proceeded in good yields

A Direct Approach to a 6‑Hetarylamino[1,2,4]triazolo[4,3‑<i>b</i>][1,2,4,5]tetrazine Library

The synthesis of 6-hetarylamino­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines is reported. The functionalized secondary amines were constructed via a K₂CO₃-mediated S_NAr reaction of weakly basic hetarylamines with 3-(3,5-dimethylpyrazol-1-yl)­[1,2,4]­triazolo­[4,3-<i>b</i>]­[1,2,4,5]­tetrazines, which allowed displacement 3,5-dimethylpyrazolyl leaving group. Significantly, the reaction exhibited a broad substrate scope and proceeded in good yields