5-Aryl-2-(3,5-dialkyl-4-hydroxyphenyl)-4,4-dimethyl-4-imidazole 3-Oxides and Their Redox Species: How Antioxidant Activity of 1-Hydroxy-2,5-dihydro-1-imidazoles Correlates with the Stability of Hybrid Phenoxyl-Nitroxides.

Cyclic nitrones of the imidazole series, containing a sterically hindered phenol group, are promising objects for studying antioxidant activity; on the other hand, they can form persistent hybrid phenoxyl-nitroxyl radicals (HPNs) upon oxidation. Here, a series of 5-aryl-4,4-dimethyl-4-imidazole 3-oxides was obtained by condensation of aromatic 2-hydroxylaminoketones with 4-formyl-2,6-dialkylphenols followed by oxidation of the initially formed -hydroxy derivatives. It was shown that the antioxidant activity of both 1-hydroxy-2,5-dihydroimidazoles and 4-imidazole 3-oxides increases with a decrease in steric volume of the alkyl substituent in the phenol group, while the stability of the corresponding HPNs generated from 4-imidazole 3-oxides reveals the opposite tendency.

The Suzuki-Miyaura reaction as a tool for modification of phenoxyl-nitroxyl radicals of the 4-imidazole -oxide series.

2-(3,5-Di--butyl-4-hydroxyphenyl)-5-(4-iodophenyl)-4,4-dimethyl-4-imidazole 3-oxide reacts with phenylboronic acid and its substituted derivatives in a cross-coupling reaction of the Suzuki-Miyaura type to form 5-biphenyl derivatives of 4-imidazole--oxide. Interaction of the same compound with B(pin) in the presence of PdCl(PPh) proceeds through the formation of intermediate 1,3,2-dioxoborolane and leads to the product of homocoupling: biphenyl-bis(imidazole). Oxidation of the resultant imidazoles with lead dioxide quantitatively yields stable conjugated phenoxyl-nitroxyl mono- and diradicals, which are of interest as electroactive paramagnetic materials.

Dual effects of indoleamine 2,3-dioxygenase inhibitors on the therapeutic effects of cyclophosphamide and cycloplatam on Ehrlich ascites tumor in mice.

Ethyl pyruvate, an inhibitor of indoleamine 2,3-dioxygenase, slightly suppressed the growth of transplantable Ehrlich tumor in mice and significantly potentiated the therapeutic effect of cyclophosphamide. Another inhibitor amidoxime produced a similar effect. However, both ethyl pyruvate and amidoxime significantly reduced the effect of cycloplatam therapy.